US20020076780A1

US20020076780A1 - Novel human ion channel proteins and polynucleotides encoding the same

Info

Publication number: US20020076780A1
Application number: US09/930,871
Authority: US
Inventors: C. Turner; Daniel Mathur; Brian Mathur
Original assignee: Lexicon Genetics Inc
Current assignee: Lexicon Pharmaceuticals Inc
Priority date: 2000-08-16
Filing date: 2001-08-14
Publication date: 2002-06-20
Also published as: WO2002014498A2; WO2002014498A3; US20050089962A1; AU2001286508A1

Abstract

Novel human polynucleotide and polypeptide sequences are disclosed that can be used in therapeutic, diagnostic, and pharmacogenomic applications.

Description

The present application claims the benefit of U.S. Provisional Application No. 60/225,989 which was filed on Aug. 16, 2000 and is herein incorporated by reference in its entirety.[0001]

1. INTRODUCTION

The present invention relates to the discovery, identification, and characterization of novel human polynucleotides encoding proteins that share sequence similarity with mammalian ion channel proteins. The invention encompasses the described polynucleotides, host cell expression systems, the encoded proteins, fusion proteins, polypeptides and peptides, antibodies to the encoded proteins and peptides, and genetically engineered animals that either lack or over express the disclosed genes, antagonists and agonists of the proteins, and other compounds that modulate the expression or activity of the proteins encoded by the disclosed genes that can be used for diagnosis, drug screening, clinical trial monitoring, or the treatment of diseases and disorders.

2. BACKGROUND OF THE INVENTION

Ion channel proteins are integral membrane proteins that mediate or facilitate the passage of materials across the lipid bilayer. Given that ion transport has been identified as an important regulator of mammalian physiology, ion channel proteins are proven drug targets.

3. SUMMARY OF THE INVENTION

The present invention relates to the discovery, identification, and characterization of nucleotides that encode novel human proteins, and the corresponding amino acid sequences of these proteins. The novel human proteins (NHPs) described for the first time herein share structural similarity with mammalian ion channel proteins, and particularly sodium channel proteins, and voltage-gated sodium channel proteins.

The novel human nucleic acid sequences described herein, encode proteins/open reading frames (ORFs) of 1998, 1962, 1442, 1381, 1387, 2009, 1973, 1453, 1392, and 1398 amino acids in length (see respectively, SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20).

The invention also encompasses agonists and antagonists of the described NHPs, including small molecules, large molecules, mutant NHPs, or portions thereof that compete with native NHP, NHP peptides, and antibodies to the NHP, as well as nucleotide sequences that can be used to inhibit the expression of the described NHP (e.g., antisense and ribozyme molecules, and gene or regulatory sequence replacement constructs) or to enhance the expression of the described NHP ORF (e.g., expression constructs that place the described gene under the control of a strong promoter system), and transgenic animals that express a NHP transgene, or “knock-outs” (which can be conditional) that do not express a functional NHP.

Further, the present invention also relates to processes for identifying compounds that modulate, i.e., act as agonists or antagonists, of NHP expression and/or NHP activity that utilize purified preparations of the described NHPs and/or NHP product, or cells expressing the same. Such compounds can be used as therapeutic agents for the treatment of any of a wide variety of symptoms associated with biological disorders or imbalances.

4. DESCRIPTION OF THE SEQUENCE LISTING AND FIGURES

The Sequence Listing provides the sequences of the NHP ORFs encoding the described NHP amino acid sequences.

5. DETAILED DESCRIPTION OF THE INVENTION

The NHPs, described for the first time herein, are novel proteins that can be found expressed in, inter alia, human cell lines, human fetal brain, brain, pituitary, cerebellum, spinal cord, thymus, spleen, lymph node, bone marrow, trachea, lung, kidney, fetal liver, liver, prostate, testis, thyroid, pancreas, salivary gland, stomach, small intestine, colon, skeletal muscle, heart, uterus, placenta, mammary gland, adrenal gland, hypothalamus, adipose, esophagus, bladder, cervix, pericardium, ovary, fetal kidney, fetal lung, and mammalian gene trapped cells. [0009]
The present invention encompasses the nucleotides presented in the Sequence Listing, host cells expressing such nucleotides, the expression products of such nucleotides, and: (a) nucleotides that encode mammalian homologs of the described genes, including the specifically described NHP, and the NHP products; (b) nucleotides that encode one or more portions of the NHP that correspond to functional domains, and the polypeptide products specified by such nucleotide sequences, including but not limited to the novel regions of any active domain(s); (c) isolated nucleotides that encode mutant versions, engineered or naturally occurring, of a NHP in which all or a part of at least one domain is deleted or altered, and the polypeptide products specified by such nucleotide sequences, including but not limited to soluble proteins and peptides in which all or a portion of the signal sequence is deleted; (d) nucleotides that encode chimeric fusion proteins containing all or a portion of a coding region of NHP, or one of its domains (e.g., a receptor or ligand binding domain, accessory protein/self-association domain, etc.) fused to another peptide or polypeptide; or (e) therapeutic or diagnostic derivatives of the described polynucleotides such as oligonucleotides, antisense polynucleotides, ribozymes, dsRNA, or gene therapy constructs comprising a sequence first disclosed in the Sequence Listing. [0010]
As discussed above, the present invention includes: (a) the human DNA sequences presented in the Sequence Listing (and vectors comprising the same) and additionally contemplates any nucleotide sequence encoding a contiguous NHP open reading frame (ORF) that hybridizes to a complement of a DNA sequence presented in the Sequence Listing under highly stringent conditions, e.g., hybridization to filter-bound DNA in 0.5 M NaHPO[0011] ₄, 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C., and washing in 0.1×SSC/0.1% SDS at 68° C. (Ausubel F. M. et al., eds., 1989, Current Protocols in Molecular Biology, Vol. I, Green Publishing Associates, Inc., and John Wiley & sons, Inc., New York, at p. 2.10.3) and encodes a functionally equivalent gene product. Additionally contemplated are any nucleotide sequences that hybridize to the complement of a DNA sequence that encodes and expresses an amino acid sequence presented in the Sequence Listing under moderately stringent conditions, e.g., washing in 0.2×SSC/0.1% SDS at 42° C. (Ausubel et al., 1989, supra), yet still encodes a functionally equivalent NHP product. Functional equivalents of a NHP include naturally occurring NHPs present in other species and mutant NHPs whether naturally occurring or engineered (by site directed mutagenesis, gene shuffling, directed evolution as described in, for example, U.S. Pat. No. 5,837,458). The invention also includes degenerate nucleic acid variants of the disclosed NHP polynucleotide sequences.
Additionally contemplated are polynucleotides encoding a NHP ORF, or its functional equivalent, encoded by polynucleotide sequences that are about 99, 95, 90, or about 85 percent similar or identical to corresponding regions of the nucleotide sequences of the Sequence Listing (as measured by BLAST sequence comparison analysis using, for example, the GCG sequence analysis package using standard default settings). [0012]
The invention also includes nucleic acid molecules, preferably DNA molecules, that hybridize to, and are therefore the complements of, the described NHP gene (or coding region) nucleotide sequences. Such hybridization conditions may be highly stringent or less highly stringent, as described above. In instances where the nucleic acid molecules are deoxyoligonucleotides (“DNA oligos”), such molecules are generally about 16 to about 100 bases long, or about 20 to about 80, or about 34 to about 45 bases long, or any variation or combination of sizes represented therein that incorporate a contiguous region of sequence first disclosed in the Sequence Listing. Such oligonucleotides can be used in conjunction with the polymerase chain reaction (PCR) to screen libraries, isolate clones, and prepare cloning and sequencing templates, etc.. [0013]
Alternatively, such NHP oligonucleotides can be used as hybridization probes for screening libraries, and assessing gene expression patterns (particularly using a micro array or high-throughput “chip” format). Additionally, a series of the described NHP oligonucleotide sequences, or the complements thereof, can be used to represent all or a portion of the described NHP sequences. The oligonucleotides, typically between about 16 to about 40 (or any whole number within the stated range) nucleotides in length can partially overlap each other and/or the NHP sequence may be represented using oligonucleotides that do not overlap. Accordingly, the described NHP polynucleotide sequences shall typically comprise at least about two or three distinct oligonucleotide sequences of at least about 18, and preferably about 25, nucleotides in length that are each first disclosed in the described Sequence Listing. Such oligonucleotide sequences may begin at any nucleotide present within a sequence in the Sequence Listing and proceed in either a sense (5′-to-3′) orientation vis-a-vis the described sequence or in an antisense orientation. [0014]
For oligonucleotide probes, highly stringent conditions may refer, e.g., to washing in 6×SSC/0.05% sodium pyrophosphate at 37° C. (for 14-base oligos), 48° C. (for 17-base oligos), 55° C. (for 20-base oligos), and 60° C. (for 23-base oligos). These nucleic acid molecules may encode or act as NHP gene antisense molecules, useful, for example, in NHP gene regulation (for and/or as antisense primers in amplification reactions of NHP gene nucleic acid sequences). With respect to NHP gene regulation, such techniques can be used to regulate biological functions. Further, such sequences may be used as part of ribozyme and/or triple helix sequences that are also useful for NHP gene regulation. [0015]
Inhibitory antisense or double stranded oligonucleotides can additionally comprise at least one modified base moiety which is selected from the group including but not limited to 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xantine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine,inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine,5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. [0016]
The antisense oligonucleotide can also comprise at least one modified sugar moiety selected from the group including but not limited to arabinose, 2-fluoroarabinose, xylulose, and hexose. [0017]
In yet another embodiment, the antisense oligonucleotide will comprise at least one modified phosphate backbone selected from the group consisting of a phosphorothioate, a phosphorodithioate, a phosphoramidothioate, a phosphoramidate, a phosphordiamidate, a methylphosphonate, an alkyl phosphotriester, and a formacetal or analog thereof. [0018]
In yet another embodiment, the antisense oligonucleotide is an a-anomeric oligonucleotide. An α-anomeric oligonucleotide forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other (Gautier et al., 1987, Nucl. Acids Res. 15:6625-6641). The oligonucleotide is a 2′-0-methylribonucleotide (Inoue et al., 1987, Nucl. Acids Res. 15:6131-6148), or a chimeric RNA-DNA analogue (Inoue et al., 1987, FEBS Lett. 215:327-330). Alternatively, double stranded RNA can be used to disrupt the expression and function of a targeted NHP. Oligonucleotides of the invention can be synthesized by standard methods known in the art, e.g. by use of an automated DNA synthesizer (such as are commercially available from Biosearch, Applied Biosystems, etc.). As examples, phosphorothioate oligonucleotides can be synthesized by the method of Stein et al. (1988, Nucl. Acids Res. 16:3209), and methylphosphonate oligonucleotides can be prepared by use of controlled pore glass polymer supports (Sarin et al., 1988, Proc. Natl. Acad. Sci. U.S.A. 85:7448-7451), etc. [0019]
Low stringency conditions are well known to those of skill in the art, and will vary predictably depending on the specific organisms from which the library and the labeled sequences are derived. For guidance regarding such conditions see, for example, Sambrook et al., 1989, Molecular Cloning, A Laboratory Manual (and periodic updates thereof), Cold Springs Harbor Press, N.Y.; and Ausubel et al., 1989, Current Protocols in Molecular Biology, Green Publishing Associates and Wiley Interscience, N.Y. [0020]
Alternatively, suitably labeled NHP nucleotide probes can be used to screen a human genomic library using appropriately stringent conditions or by PCR. The identification and characterization of human genomic clones is helpful for identifying polymorphisms (including, but not limited to, nucleotide repeats, microsatellite alleles, single nucleotide polymorphisms, or coding single nucleotide polymorphisms), determining the genomic structure of a given locus/allele, and designing diagnostic tests. For example, sequences derived from regions adjacent to the intron/exon boundaries of the human gene can be used to design primers for use in amplification assays to detect mutations within the exons, introns, splice sites (e.g., splice acceptor and/or donor sites), etc., that can be used in diagnostics and pharmacogenomics. [0021]
Further, a NHP gene homolog can be isolated from nucleic acid from an organism of interest by performing PCR using two degenerate or “wobble” oligonucleotide primer pools designed on the basis of amino acid sequences within the NHP products disclosed herein. The template for the reaction may be total RNA, mRNA, and/or cDNA obtained by reverse transcription of mRNA prepared from human or non-human cell lines or tissue known or suspected to express an allele of a NHP gene. The PCR product can be subcloned and sequenced to ensure that the amplified sequences represent the sequence of the desired NHP gene. The PCR fragment can then be used to isolate a full length cDNA clone by a variety of methods. For example, the amplified fragment can be labeled and used to screen a cDNA library, such as a bacteriophage cDNA library. Alternatively, the labeled fragment can be used to isolate genomic clones via the screening of a genomic library. [0022]
PCR technology can also be used to isolate full length cDNA sequences. For example, RNA can be isolated, following standard procedures, from an appropriate cellular or tissue source (i.e., one known, or suspected, to express a NHP gene). A reverse transcription (RT) reaction can be performed on the RNA using an oligonucleotide primer specific for the most 5′ end of the amplified fragment for the priming of first strand synthesis. The resulting RNA/DNA hybrid may then be “tailed” using a standard terminal transferase reaction, the hybrid may be digested with RNase H, and second strand synthesis may then be primed with a complementary primer. Thus, cDNA sequences upstream of the amplified fragment can be isolated. For a review of cloning strategies that can be used, see e.g., Sambrook et al., 1989, supra. [0023]
A cDNA encoding a mutant NHP gene can be isolated, for example, by using PCR. In this case, the first cDNA strand may be synthesized by hybridizing an oligo-dT oligonucleotide to mRNA isolated from tissue known or suspected to be expressed in an individual putatively carrying a mutant NHP allele, and by extending the new strand with reverse transcriptase. The second strand of the cDNA is then synthesized using an oligonucleotide that hybridizes specifically to the 5′ end of the normal gene. Using these two primers, the product is then amplified via PCR, optionally cloned into a suitable vector, and subjected to DNA sequence analysis through methods well known to those of skill in the art. By comparing the DNA sequence of the mutant NHP allele to that of a corresponding normal NHP allele, the mutation(s) responsible for the loss or alteration of function of the mutant NHP gene product can be ascertained. [0024]
Alternatively, a genomic library can be constructed using DNA obtained from an individual suspected of or known to carry a mutant NHP allele (e.g., a person manifesting a NHP-associated phenotype such as, for example, obesity, high blood pressure, connective tissue disorders, infertility, diabetes, alopecia, arrhythmia, etc.), or a cDNA library can be constructed using RNA from a tissue known, or suspected, to express a mutant NHP allele. A normal NHP gene, or any suitable fragment thereof, can then be labeled and used as a probe to identify the corresponding mutant NHP allele in such libraries. Clones containing mutant NHP gene sequences can then be purified and subjected to sequence analysis according to methods well known to those skilled in the art. [0025]
Additionally, an expression library can be constructed utilizing cDNA synthesized from, for example, RNA isolated from a tissue known, or suspected, to express a mutant NHP allele in an individual suspected of or known to carry such a mutant allele. In this manner, gene products made by the putatively mutant tissue can be expressed and screened using standard antibody screening techniques in conjunction with antibodies raised against a normal NHP product, as described below. (For screening techniques, see, for example, Harlow, E. and Lane, eds., 1988, “Antibodies: A Laboratory Manual”, Cold Spring Harbor Press, Cold Spring Harbor.) Additionally, screening can be accomplished by screening with labeled NHP fusion proteins, such as, for example, AP-NHP or NHP-AP fusion proteins. In cases where a NHP mutation results in an expressed gene product with altered function (e.g., as a result of a missense or a frameshift mutation), polyclonal antibodies to a NHP are likely to cross-react with a corresponding mutant NHP gene product. Library clones detected via their reaction with such labeled antibodies can be purified and subjected to sequence analysis according to methods well known in the art. [0026]
The invention also encompasses (a) DNA vectors that contain any of the foregoing NHP coding sequences and/or their complements (i.e., antisense); (b) DNA expression vectors that contain any of the foregoing NHP coding sequences operatively associated with a regulatory element that directs the expression of the coding sequences (for example, baculo virus as described in U.S. Pat. No. 5,869,336 herein incorporated by reference); (c) genetically engineered host cells that contain any of the foregoing NHP coding sequences operatively associated with a regulatory element that directs the expression of the coding sequences in the host cell; and (d) genetically engineered host cells that express an endogenous NHP gene under the control of an exogenously introduced regulatory element (i.e., gene activation). As used herein, regulatory elements include but are not limited to inducible and non-inducible promoters, enhancers, operators and other elements known to those skilled in the art that drive and regulate expression. Such regulatory elements include but are not limited to the cytomegalovirus hCMV immediate early gene, regulatable, viral (particularly retroviral LTR promoters) the early or late promoters of SV40 adenovirus, the lac system, the trp system, the TAC system, the tet system, the TRC system, the major operator and promoter regions of phage lambda, the control regions of fd coat protein, the promoter for 3-phosphoglycerate kinase (PGK), the promoters of acid phosphatase, and the promoters of the yeast α-mating factors. [0027]
The present invention also encompasses antibodies and anti-idiotypic antibodies (including Fab fragments), antagonists and agonists of the NHP, as well as compounds or nucleotide constructs that inhibit expression of a NHP gene (transcription factor inhibitors, antisense and ribozyme molecules, or gene or regulatory sequence replacement constructs), or promote the expression of a NHP (e.g., expression constructs in which NHP coding sequences are operatively associated with expression control elements such as promoters, promoter/enhancers, etc.). [0028]
The NHP or NHP peptides, NHP fusion proteins, NHP nucleotide sequences, antibodies, antagonists and agonists can be useful for the detection of mutant NHPs or inappropriately expressed NHPs for the diagnosis of disease. The NHP proteins or peptides, NHP fusion proteins, NHP nucleotide sequences, host cell expression systems, antibodies, antagonists, agonists and genetically engineered cells and animals can be used for screening for drugs (or high throughput screening of combinatorial libraries) effective in the treatment of the symptomatic or phenotypic manifestations of perturbing the normal function of NHP in the body. The use of engineered host cells and/or animals may offer an advantage in that such systems allow not only for the identification of compounds that bind to the endogenous receptor for an NHP, but can also identify compounds that trigger NHP-mediated activities or pathways. [0029]
Finally, the NHP products can be used as therapeutics. For example, soluble derivatives such as NHP peptides/domains corresponding to a NHP, NHP fusion protein products (especially NHP-Ig fusion proteins, i.e., fusions of a NHP, or a domain of a NHP, to an IgFc), NHP antibodies and anti-idiotypic antibodies (including Fab fragments), antagonists or agonists (including compounds that modulate or act on downstream targets in a NHP-mediated pathway) can be used to directly treat diseases or disorders. For instance, the administration of an effective amount of soluble NHP, or a NHP-IgFc fusion protein or an anti-idiotypic antibody (or its Fab) that mimics the NHP could activate or effectively antagonize the endogenous NHP receptor. Nucleotide constructs encoding such NHP products can be used to genetically engineer host cells to express such products in vivo; these genetically engineered cells function as “bioreactors” in the body delivering a continuous supply of a NHP, a NHP peptide, or a NHP fusion protein to the body. Nucleotide constructs encoding functional NHPs, mutant NHPs, as well as antisense and ribozyme molecules can also be used in “gene therapy” approaches for the modulation of NHP expression. Thus, the invention also encompasses pharmaceutical formulations and methods for treating biological disorders. [0030]
Various aspects of the invention are described in greater detail in the subsections below. [0031]

5.1 THE NHP SEQUENCES

The cDNA sequences and the corresponding deduced amino acid sequences of the described NHPs are presented in the Sequence Listing. The NHP nucleotides were obtained from cDNAs generated from human brain, fetal brain, pituitary, cerebellum, testis, prostate, fetal brain, adipose mRNAs (Clontech, Palo Alto, Calif. Edge Biosystems, Gaithersburg, Md.). [0032]
Several polymorphisms were identified including an A-or-C transversion in the sequence region corresponding to, for example, nucleotide number 2,941 of SEQ ID NO:1 which can result in either a leu or met being present in the corresponding amino acid sequence region represented by, for example, amino acid position number 981 of SEQ ID NO:2, and a A-or-G transition in the sequence region corresponding to, for example, nucleotide number 3,166 of SEQ ID NO:1 which can result in either a thr or ala being present in the corresponding amino acid sequence region represented by, for example, amino acid position number 1,056 of SEQ ID NO:2. [0033]

5.2 THE NHP AND NHP POLYPEPTIDES

The described NHPs, NHP polypeptides, peptide fragments, mutated, truncated, or deleted forms of the NHPs, and/or NHP fusion proteins can be prepared for a variety of uses, including but not limited to the generation of antibodies, as reagents in diagnostic assays, the identification of other cellular gene products related to NHP, as reagents in assays for screening for compounds that can be used as pharmaceutical reagents useful in the therapeutic treatment of mental, biological, or medical disorders and diseases. Given the similarity information and expression data, the described NHP can be targeted (by drugs, oligos, antibodies, etc,) in order to treat disease, or to therapeutically augment the efficacy of, for example, chemotherapeutic agents. [0034]
The Sequence Listing discloses the amino acid sequence encoded by the described NHP ORF. The NHPs display initiator methionines in DNA sequence contexts consistent with translation initiation sites. [0035]
The NHP amino acid sequences of the invention includes the amino acid sequence presented in the Sequence Listing as well as analogues and derivatives thereof. Further, corresponding NHP homologues from other species are encompassed by the invention. In fact, any NHP proteins encoded by the NHP nucleotide sequences described above are within the scope of the invention, as are any novel polynucleotide sequences encoding all or any novel portion of an amino acid sequence presented in the Sequence Listing. The degenerate nature of the genetic code is well known, and, accordingly, each amino acid presented in the Sequence Listing, is generically representative of the well known nucleic acid “triplet” codon, or in many cases codons, that can encode the amino acid. As such, as contemplated herein, the amino acid sequences presented in the Sequence Listing, when taken together with the genetic code (see, for example, Table 4-1 at page 109 of “Molecular Cell Biology”, 1986, J. Darnell et al. eds., Scientific American Books, New York, N.Y., herein incorporated by reference) are generically representative of all the various permutations and combinations of nucleic acid sequences that can encode such amino acid sequences. [0036]
The invention also encompasses proteins that are functionally equivalent to the NHP encoded by the presently described nucleotide sequences as judged by any of a number of criteria, including, but not limited to, the ability to bind and cleave a substrate of a NHP, or the ability to effect an identical or complementary downstream pathway, or a change in cellular metabolism (e.g., proteolytic activity, ion flux, tyrosine phosphorylation, etc.). Such functionally equivalent NHP products include, but are not limited to, additions or substitutions of amino acid residues within the amino acid sequence encoded by the NHP nucleotide sequences described above, but which result in a silent change, thus producing a functionally equivalent gene product. Amino acid substitutions can be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid. [0037]
A variety of host-expression vector systems can be used to express the NHP nucleotide sequences of the invention. Where, as in the present instance, the NHP peptide or polypeptide is thought to be membrane protein, the hydrophobic regions of the protein can be excised and the resulting soluble peptide or polypeptide can be recovered from the culture media. Such expression systems also encompass engineered host cells that express a NHP, or functional equivalent, in situ. Purification or enrichment of a NHP from such expression systems can be accomplished using appropriate detergents and lipid micelles and methods well known to those skilled in the art. However, such engineered host cells themselves may be used in situations where it is important not only to retain the structural and functional characteristics of the NHP, but to assess biological activity, e.g., in drug screening assays. [0038]
The expression systems that may be used for purposes of the invention include but are not limited to microorganisms such as bacteria (e.g., [0039] E. coli, B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing NHP nucleotide sequences; yeast (e.g., Saccharomyces, Pichia) transformed with recombinant yeast expression vectors containing NHP nucleotide sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing NHP sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing NHP nucleotide sequences; or mammalian cell systems (e.g., COS, CHO, BHK, 293, 3T3) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter).
In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the NHP product being expressed. For example, when a large quantity of such a protein is to be produced for the generation of pharmaceutical compositions of or containing NHP, or for raising antibodies to a NHP, vectors that direct the expression of high levels of fusion protein products that are readily purified may be desirable. Such vectors include, but are not limited, to the [0040] E. coli expression vector pUR278 (Ruther et al., 1983, EMBO J. 2:1791), in which a NHP coding sequence may be ligated individually into the vector in frame with the lacZ coding region so that a fusion protein is produced; pIN vectors (Inouye & Inouye, 1985, Nucleic Acids Res. 13:3101-3109; Van Heeke & Schuster, 1989, J. Biol. Chem. 264:5503-5509); and the like. pGEX vectors (Pharmacia or American Type Culture Collection) can also be used to express foreign polypeptides as fusion proteins with glutathione S-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to glutathione-agarose beads followed by elution in the presence of free glutathione. The PGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target gene product can be released from the GST moiety.
In an insect system, [0041] Autographa californica nuclear polyhidrosis virus (AcNPV) is used as a vector to express foreign genes. The virus grows in Spodoptera frugiperda cells. A NHP gene coding sequence may be cloned individually into non-essential regions (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter). Successful insertion of NHP gene coding sequence will result in inactivation of the polyhedrin gene and production of non-occluded recombinant virus (i.e., virus lacking the proteinaceous coat coded for by the polyhedrin gene). These recombinant viruses are then used to infect Spodoptera frugiperda cells in which the inserted gene is expressed (e.g., see Smith et al., 1983, J. Virol. 46:584; Smith, U.S. Pat. No. 4,215,051).
In mammalian host cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, the NHP nucleotide sequence of interest may be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric gene may then be inserted in the adenovirus genome by in vitro or in vivo recombination. Insertion in a non-essential region of the viral genome (e.g., region E1 or E3) will result in a recombinant virus that is viable and capable of expressing a NHP product in infected hosts (e.g., See Logan & Shenk, 1984, Proc. Natl. Acad. Sci. USA 81:3655-3659). Specific initiation signals may also be required for efficient translation of inserted NHP nucleotide sequences. These signals include the ATG initiation codon and adjacent sequences. In cases where an entire NHP gene or cDNA, including its own initiation codon and adjacent sequences, is inserted into the appropriate expression vector, no additional translational control signals may be needed. However, in cases where only a portion of a NHP coding sequence is inserted, exogenous translational control signals, including, perhaps, the ATG initiation codon, must be provided. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (See Bitter et al., 1987, Methods in Enzymol. 153:516-544). [0042]
In addition, a host cell strain may be chosen that modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the foreign protein expressed. To this end, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used. Such mammalian host cells include, but are not limited to, CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3, WI38, and in particular, human cell lines. [0043]
For long-term, high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines which stably express the NHP sequences described above can be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines. This method may advantageously be used to engineer cell lines which express the NHP product. Such engineered cell lines may be particularly useful in screening and evaluation of compounds that affect the endogenous activity of the NHP product. [0044]
A number of selection systems may be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler, et al., 1977, Cell 11:223), hypoxanthine-guanine phosphoribosyltransferase (Szybalska & Szybalski, 1962, Proc. Natl. Acad. Sci. USA 48:2026), and adenine phosphoribosyltransferase (Lowy, et al., 1980, Cell 22:817) genes can be employed in tk[0045] ⁻, hgprt⁻ or aprt⁻ cells, respectively. Also, antimetabolite resistance can be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler, et al., 1980, Natl. Acad. Sci. USA 77:3567; O'Hare, et al., 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Colberre-Garapin, et al., 1981, J. Mol. Biol. 150:1); and hygro, which confers resistance to hygromycin (Santerre, et al., 1984, Gene 30:147).
Alternatively, any fusion protein can be readily purified by utilizing an antibody specific for the fusion protein being expressed. For example, a system described by Janknecht et al. allows for the ready purification of non-denatured fusion proteins expressed in human cell lines (Janknecht, et al., 1991, Proc. Natl. Acad. Sci. USA 88:8972-8976). In this system, the gene of interest is subcloned into a vaccinia recombination plasmid such that the gene's open reading frame is translationally fused to an amino-terminal tag consisting of six histidine residues. Extracts from cells infected with recombinant vaccinia virus are loaded onto Ni[0046] ²⁺. nitriloacetic acid-agarose columns and histidine-tagged proteins are selectively eluted with imidazole-containing buffers.
Additionally contemplated are oligopeptides that are modeled on an amino acid sequence first described in the Sequence Listing. Such NHP oligopeptides are generally between about 10 to about 100 amino acids long, or between about 16 to about 80, or between about 20 to about 35 amino acids long, or any variation or combination of sizes represented therein that incorporate a contiguous region of sequence first disclosed in the Sequence Listing. Such NHP oligopeptides can be of any length disclosed within the above ranges and can initiate at any amino acid position represented in the Sequence Listing. [0047]

5.3 ANTIBODIES TO NHP PRODUCTS

Antibodies that specifically recognize one or more epitopes of a NHP, or epitopes of conserved variants of a NHP, or peptide fragments of a NHP are also encompassed by the invention. Such antibodies include but are not limited to polyclonal antibodies, monoclonal antibodies (mAbs), humanized or chimeric antibodies, single chain antibodies, Fab fragments, F(ab′)[0048] ₂fragments, fragments produced by a Fab expression library, anti-idiotypic (anti-Id) antibodies, and epitope-binding fragments of any of the above.
The antibodies of the invention may be used, for example, in the detection of NHP in a biological sample and may, therefore, be utilized as part of a diagnostic or prognostic technique whereby patients may be tested for abnormal amounts of NHP. Such antibodies may also be utilized in conjunction with, for example, compound screening schemes for the evaluation of the effect of test compounds on expression and/or activity of a NHP gene product. Additionally, such antibodies can be used in conjunction gene therapy to, for example, evaluate the normal and/or engineered NHP-expressing cells prior to their introduction into the patient. Such antibodies may additionally be used as a method for the inhibition of abnormal NHP activity. Thus, such antibodies may, therefore, be utilized as part of treatment methods. [0049]
For the production of antibodies, various host animals may be immunized by injection with the NHP, an NHP peptide (e.g., one corresponding to a functional domain of an NHP), truncated NHP polypeptides (NHP in which one or more domains have been deleted), functional equivalents of the NHP or mutated variant of the NHP. Such host animals may include but are not limited to pigs, rabbits, mice, goats, and rats, to name but a few. Various adjuvants may be used to increase the immunological response, depending on the host species, including but not limited to Freund's (complete and incomplete), mineral gels such as aluminum hydroxide, surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, keyhole limpet hemocyanin, dinitrophenol, and potentially useful human adjuvants such as BCG (bacille Calmette-Guerin) and Corynebacterium parvum. Polyclonal antibodies are heterogeneous populations of antibody molecules derived from the sera of the immunized animals. [0050]
Monoclonal antibodies, which are homogeneous populations of antibodies to a particular antigen, can be obtained by any technique which provides for the production of antibody molecules by continuous cell lines in culture. These include, but are not limited to, the hybridoma technique of Kohler and Milstein, (1975, Nature 256:495-497; and U.S. Pat. No. 4,376,110), the human B-cell hybridoma technique (Kosbor et al., 1983, Immunology Today 4:72; Cole et al., 1983, Proc. Natl. Acad. Sci. USA 80:2026-2030), and the EBV-hybridoma technique (Cole et al., 1985, Monoclonal Antibodies And Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Such antibodies may be of any immunoglobulin class including IgG, IgM, IgE, IgA, IgD and any subclass thereof. The hybridoma producing the mAb of this invention may be cultivated in vitro or in vivo. Production of high titers of mabs in vivo makes this the presently preferred method of production. [0051]
In addition, techniques developed for the production of “chimeric antibodies” (Morrison et al., 1984, Proc. Natl. Acad. Sci., 81:6851-6855; Neuberger et al., 1984, Nature, 312:604-608; Takeda et al., 1985, Nature, 314:452-454) by splicing the genes from a mouse antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity can be used. A chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived from a murine mAb and a human immunoglobulin constant region. [0052]
Alternatively, techniques described for the production of single chain antibodies (U.S. Pat. No. 4,946,778; Bird, 1988, Science 242:423-426; Huston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; and Ward et al., 1989, Nature 341:544-546) can be adapted to produce single chain antibodies against NHP gene products. Single chain antibodies are formed by linking the heavy and light chain fragments of the Fv region via an amino acid bridge, resulting in a single chain polypeptide. [0053]
Antibody fragments that recognize specific epitopes may be generated by known techniques. For example, such fragments include, but are not limited to: the F(ab′)[0054] ₂fragments which can be produced by pepsin digestion of the antibody molecule and the Fab fragments which can be generated by reducing the disulfide bridges of the F(ab′)₂fragments. Alternatively, Fab expression libraries may be constructed (Huse et al., 1989, Science, 246:1275-1281) to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity.
Antibodies to a NHP can, in turn, be utilized to generate anti-idiotype antibodies that “mimic” a given NHP, using techniques well known to those skilled in the art. (See, e.g., Greenspan & Bona, 1993, FASEB J 7(5):437-444; and Nissinoff, 1991, J. Immunol. 147(8) :2429-2438). For example antibodies which bind to a NHP domain and competitively inhibit the binding of NHP to its cognate receptor can be used to generate anti-idiotypes that “mimic” the NHP and, therefore, bind and activate or neutralize a receptor. Such anti-idiotypic antibodies or Fab fragments of such anti-idiotypes can be used in therapeutic regimens involving a NHP mediated pathway. [0055]
The present invention is not to be limited in scope by the specific embodiments described herein, which are intended as single illustrations of individual aspects of the invention, and functionally equivalent methods and components are within the scope of the invention. Indeed, various modifications of the invention, in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims. All cited publications, patents, and patent applications are herein incorporated by reference in their entirety. [0056]
1 20 1 5997 DNA homo sapiens 1 atggagcaaa cagtgcttgt accaccagga cctgacagct tcaacttctt caccagagaa 60 tctcttgcgg ctattgaaag acgcattgca gaagaaaagg caaagaatcc caaaccagac 120 aaaaaagatg acgacgaaaa tggcccaaag ccaaatagtg acttggaagc tggaaagaac 180 cttccattta tttatggaga cattcctcca gagatggtgt cagagcccct ggaggacctg 240 gacccctact atatcaataa gaaaactttt atagtattga ataaagggaa ggccatcttc 300 cggttcagtg ccacctctgc cctgtacatt ttaactccct tcaatcctct taggaaaata 360 gctattaaga ttttggtaca ttcattattc agcatgctaa ttatgtgcac tattttgaca 420 aactgtgtgt ttatgacaat gagtaaccct cctgattgga caaagaatgt agaatacacc 480 ttcacaggaa tatatacttt tgaatcactt ataaaaatta ttgcaagggg attctgttta 540 gaagatttta ctttccttcg ggatccatgg aactggctcg atttcactgt cattacattt 600 gcgtacgtca cagagtttgt ggacctgggc aatgtctcgg cattgagaac attcagagtt 660 ctccgagcat tgaagacgat ttcagtcatt ccaggcctga aaaccattgt gggagccctg 720 atccagtctg tgaagaagct ctcagatgta atgatcctga ctgtgttctg tctgagcgta 780 tttgctctaa ttgggctgca gctgttcatg ggcaacctga ggaataaatg tatacaatgg 840 cctcccacca atgcttcctt ggaggaacat agtatagaaa agaatataac tgtgaattat 900 aatggtacac ttataaatga aactgtcttt gagtttgact ggaagtcata tattcaagat 960 tcaagatatc attatttcct ggagggtttt ttagatgcac tactatgtgg aaatagctct 1020 gatgcaggcc aatgtccaga gggatatatg tgtgtgaaag ctggtagaaa tcccaattat 1080 ggctacacaa gctttgatac cttcagttgg gcttttttgt ccttgtttcg actaatgact 1140 caggacttct gggaaaatct ttatcaactg acattacgtg ctgctgggaa aacgtacatg 1200 atattttttg tgttggtcat tttcttgggc tcattctacc taataaattt gatcctggct 1260 gtggtggcca tggcctacga ggaacagaat caggccacct tggaagaagc agaacagaaa 1320 gaggccgaat ttcagcagat gattgaacag cttaaaaagc aacaggaggc agctcagcag 1380 gcagcaacgg caactgcctc agaacattcc agagagccca gtgcagcagg caggctctca 1440 gacagctcat ctgaagcctc taagttgagt tccaagagtg ctaaggaaag aagaaatcgg 1500 aggaagaaaa gaaaacagaa agagcagtct ggtggggaag agaaagatga ggatgaattc 1560 caaaaatctg aatctgagga cagcatcagg aggaaaggtt ttcgcttctc cattgaaggg 1620 aaccgattga catatgaaaa gaggtactcc tccccacacc agtctttgtt gagcatccgt 1680 ggctccctat tttcaccaag gcgaaatagc agaacaagcc ttttcagctt tagagggcga 1740 gcaaaggatg tgggatctga gaacgacttc gcagatgatg agcacagcac ctttgaggat 1800 aacgagagcc gtagagattc cttgtttgtg ccccgacgac acggagagag acgcaacagc 1860 aacctgagtc agaccagtag gtcatcccgg atgctggcag tgtttccagc gaatgggaag 1920 atgcacagca ctgtggattg caatggtgtg gtttccttgg ttggtggacc ttcagttcct 1980 acatcgcctg ttggacagct tctgccagag ggaacaacca ctgaaactga aatgagaaag 2040 agaaggtcaa gttctttcca cgtttccatg gactttctag aagatccttc ccaaaggcaa 2100 cgagcaatga gtatagccag cattctaaca aatacagtag aagaacttga agaatccagg 2160 cagaaatgcc caccctgttg gtataaattt tccaacatat tcttaatctg ggactgttct 2220 ccatattggt taaaagtgaa acatgttgtc aacctggtyg tgatggaccc atttgttgac 2280 ctggccatca ccatctgtat tgtcttaaat actcttttca tggccatgga gcactatcca 2340 atgacggacc atttcaataa tgtgcttaca gtaggaaact tggttttcac tgggatcttt 2400 acagcagaaa tgtttctgaa aattattgcc atggatcctt actattattt ccaagaaggc 2460 tggaatatct ttgacggttt tattgtgacg cttagcctgg tagaacttgg actcgccaat 2520 gtggaaggat tatctgttct ccgttcattt cgattgctgc gagttttcaa gttggcaaaa 2580 tcttggccaa cgttaaatat gctaataaag atcatcggca attccgtggg ggctctggga 2640 aatttaaccc tcgtcttggc catcatcgtc ttcatttttg ccgtggtcgg catgcagctc 2700 tttggtaaaa gctacaaaga ttgtgtctgc aagatcgcca gtgattgtca actcccacgc 2760 tggcacatga atgacttctt ccactccttc ctgattgtgt tccgcgtgct gtgtggggag 2820 tggatagaga ccatgtggga ctgtatggag gttgctggtc aagccatgtg ccttactgtc 2880 ttcatgatgg tcatggtgat tggaaaccta gtggtcctga atctctttct ggccttgctt 2940 mtgagctcat ttagtgcaga caaccttgca gccactgatg atgataatga aatgaataat 3000 ctccaaattg ctgtggatag gatgcacaaa ggagtagctt atgtgaaaag aaaaatatat 3060 gaatttattc aacagtcctt cattaggaaa caaaagattt tagatgaaat taaaccactt 3120 gatgatctaa acaacaagaa agacagttgt atgtccaatc atacarcaga aattgggaaa 3180 gatcttgact atcttaaaga tgtaaatgga actacaagtg gtataggaac tggcagcagt 3240 gttgaaaaat acattattga tgaaagtgat tacatgtcat tcataaacaa ccccagtctt 3300 actgtgactg taccaattgc tgtaggagaa tctgactttg aaaatttaaa cacggaagac 3360 tttagtagtg aatcggatct ggaagaaagc aaagagaaac tgaatgaaag cagtagctca 3420 tcagaaggta gcactgtgga catcggcgca cctgtagaag aacagcccgt agtggaacct 3480 gaagaaactc ttgaaccaga agcttgtttc actgaaggct gtgtacaaag attcaagtgt 3540 tgtcaaatca atgtggaaga aggcagagga aaacaatggt ggaacctgag aaggacgtgt 3600 ttccgaatag ttgaacataa ctggtttgag accttcattg ttttcatgat tctccttagt 3660 agtggtgctc tggcatttga agatatatat attgatcagc gaaagacgat taagacgatg 3720 ttggaatatg ctgacaaggt tttcacttac attttcattc tggaaatgct tctaaaatgg 3780 gtggcatatg gctatcaaac atatttcacc aatgcctggt gttggctgga cttcttaatt 3840 gttgatgttt cattggtcag tttaacagca aatgccttgg gttactcaga acttggagcc 3900 atcaaatctc tcaggacact aagagctctg agacctctaa gagccttatc tcgatttgaa 3960 gggatgaggg tggttgtgaa tgccctttta ggagcaattc catccatcat gaatgtgctt 4020 ctggtttgtc ttatattctg gctaattttc agcatcatgg gcgtaaattt gtttgctggc 4080 aaattctacc actgtattaa caccacaact ggtgacaggt ttgacatcga agacgtgaat 4140 aatcatactg attgcctaaa actaatagaa agaaatgaga ctgctcgatg gaaaaatgtg 4200 aaagtaaact ttgataatgt aggatttggg tatctctctt tgcttcaagt tgccacattc 4260 aaaggatgga tggatataat gtatgcagca gttgattcca gaaatgtgga actccagcct 4320 aagtatgaag aaagtctgta catgtatctt tactttgtta ttttcatcat ctttgggtcc 4380 ttcttcacct tgaacctgtt tattggtgtc atcatagata atttcaacca gcagaaaaag 4440 aagtttggag gtcaagacat ctttatgaca gaagaacaga agaaatacta taatgcaatg 4500 aaaaaattag gatcgaaaaa accgcaaaag cctatacctc gaccaggaaa caaatttcaa 4560 ggaatggtct ttgacttcgt aaccagacaa gtttttgaca taagcatcat gattctcatc 4620 tgtcttaaca tggtcacaat gatggtggaa acagatgacc agagtgaata tgtgactacc 4680 attttgtcac gcatcaatct ggtgttcatt gtgctattta ctggagagtg tgtactgaaa 4740 ctcatctctc tacgccatta ttattttacc attggatgga atatttttga ttttgtggtt 4800 gtcattctct ccattgtagg tatgtttctt gccgagctga tagaaaagta tttcgtgtcc 4860 cctaccctgt tccgagtgat ccgtcttgct aggattggcc gaatcctacg tctgatcaaa 4920 ggagcaaagg ggatccgcac gctgctcttt gctttgatga tgtcccttcc tgcgttgttt 4980 aacatcggcc tcctactctt cctagtcatg ttcatctacg ccatctttgg gatgtccaac 5040 tttgcctatg ttaagaggga agttgggatc gatgacatgt tcaactttga gacctttggc 5100 aacagcatga tctgcctatt ccaaattaca acctctgctg gctgggatgg attgctagca 5160 cccattctca acagtaagcc acccgactgt gaccctaata aagttaaccc tggaagctca 5220 gttaagggag actgtgggaa cccatctgtt ggaattttct tttttgtcag ttacatcatc 5280 atatccttcc tggttgtggt gaacatgtac atcgcggtca tcctggagaa cttcagtgtt 5340 gctactgaag aaagtgcaga gcctctgagt gaggatgact ttgagatgtt ctatgaggtt 5400 tgggagaagt ttgatcccga tgcaactcag ttcatggaat ttgaaaaatt atctcagttt 5460 gcagctgcgc ttgaaccgcc tctcaatctg ccacaaccaa acaaactcca gctcattgcc 5520 atggatttgc ccatggtgag tggtgaccgg atccactgtc ttgatatctt atttgctttt 5580 acaaagcggg ttctaggaga gagtggagag atggatgctc tacgaataca gatggaagag 5640 cgattcatgg cttccaatcc ttccaaggtc tcctatcagc caatcactac tactttaaaa 5700 cgaaaacaag aggaagtatc tgctgtcatt attcagcgtg cttacagacg ccacctttta 5760 aagcgaactg taaaacaagc ttcctttacg tacaataaaa acaaaatcaa aggtggggct 5820 aatcttctta taaaagaaga catgataatt gacagaataa atgaaaactc tattacagaa 5880 aaaactgatc tgaccatgtc cactgcagct tgtccacctt cctatgaccg ggtgacaaag 5940 ccaattgtgg aaaaacatga gcaagaaggc aaagatgaaa aagccaaagg gaaataa 5997 2 1998 PRT homo sapiens VARIANT (1)...(1998) Xaa = Any Amino Acid 2 Met Glu Gln Thr Val Leu Val Pro Pro Gly Pro Asp Ser Phe Asn Phe 1 5 10 15 Phe Thr Arg Glu Ser Leu Ala Ala Ile Glu Arg Arg Ile Ala Glu Glu 20 25 30 Lys Ala Lys Asn Pro Lys Pro Asp Lys Lys Asp Asp Asp Glu Asn Gly 35 40 45 Pro Lys Pro Asn Ser Asp Leu Glu Ala Gly Lys Asn Leu Pro Phe Ile 50 55 60 Tyr Gly Asp Ile Pro Pro Glu Met Val Ser Glu Pro Leu Glu Asp Leu 65 70 75 80 Asp Pro Tyr Tyr Ile Asn Lys Lys Thr Phe Ile Val Leu Asn Lys Gly 85 90 95 Lys Ala Ile Phe Arg Phe Ser Ala Thr Ser Ala Leu Tyr Ile Leu Thr 100 105 110 Pro Phe Asn Pro Leu Arg Lys Ile Ala Ile Lys Ile Leu Val His Ser 115 120 125 Leu Phe Ser Met Leu Ile Met Cys Thr Ile Leu Thr Asn Cys Val Phe 130 135 140 Met Thr Met Ser Asn Pro Pro Asp Trp Thr Lys Asn Val Glu Tyr Thr 145 150 155 160 Phe Thr Gly Ile Tyr Thr Phe Glu Ser Leu Ile Lys Ile Ile Ala Arg 165 170 175 Gly Phe Cys Leu Glu Asp Phe Thr Phe Leu Arg Asp Pro Trp Asn Trp 180 185 190 Leu Asp Phe Thr Val Ile Thr Phe Ala Tyr Val Thr Glu Phe Val Asp 195 200 205 Leu Gly Asn Val Ser Ala Leu Arg Thr Phe Arg Val Leu Arg Ala Leu 210 215 220 Lys Thr Ile Ser Val Ile Pro Gly Leu Lys Thr Ile Val Gly Ala Leu 225 230 235 240 Ile Gln Ser Val Lys Lys Leu Ser Asp Val Met Ile Leu Thr Val Phe 245 250 255 Cys Leu Ser Val Phe Ala Leu Ile Gly Leu Gln Leu Phe Met Gly Asn 260 265 270 Leu Arg Asn Lys Cys Ile Gln Trp Pro Pro Thr Asn Ala Ser Leu Glu 275 280 285 Glu His Ser Ile Glu Lys Asn Ile Thr Val Asn Tyr Asn Gly Thr Leu 290 295 300 Ile Asn Glu Thr Val Phe Glu Phe Asp Trp Lys Ser Tyr Ile Gln Asp 305 310 315 320 Ser Arg Tyr His Tyr Phe Leu Glu Gly Phe Leu Asp Ala Leu Leu Cys 325 330 335 Gly Asn Ser Ser Asp Ala Gly Gln Cys Pro Glu Gly Tyr Met Cys Val 340 345 350 Lys Ala Gly Arg Asn Pro Asn Tyr Gly Tyr Thr Ser Phe Asp Thr Phe 355 360 365 Ser Trp Ala Phe Leu Ser Leu Phe Arg Leu Met Thr Gln Asp Phe Trp 370 375 380 Glu Asn Leu Tyr Gln Leu Thr Leu Arg Ala Ala Gly Lys Thr Tyr Met 385 390 395 400 Ile Phe Phe Val Leu Val Ile Phe Leu Gly Ser Phe Tyr Leu Ile Asn 405 410 415 Leu Ile Leu Ala Val Val Ala Met Ala Tyr Glu Glu Gln Asn Gln Ala 420 425 430 Thr Leu Glu Glu Ala Glu Gln Lys Glu Ala Glu Phe Gln Gln Met Ile 435 440 445 Glu Gln Leu Lys Lys Gln Gln Glu Ala Ala Gln Gln Ala Ala Thr Ala 450 455 460 Thr Ala Ser Glu His Ser Arg Glu Pro Ser Ala Ala Gly Arg Leu Ser 465 470 475 480 Asp Ser Ser Ser Glu Ala Ser Lys Leu Ser Ser Lys Ser Ala Lys Glu 485 490 495 Arg Arg Asn Arg Arg Lys Lys Arg Lys Gln Lys Glu Gln Ser Gly Gly 500 505 510 Glu Glu Lys Asp Glu Asp Glu Phe Gln Lys Ser Glu Ser Glu Asp Ser 515 520 525 Ile Arg Arg Lys Gly Phe Arg Phe Ser Ile Glu Gly Asn Arg Leu Thr 530 535 540 Tyr Glu Lys Arg Tyr Ser Ser Pro His Gln Ser Leu Leu Ser Ile Arg 545 550 555 560 Gly Ser Leu Phe Ser Pro Arg Arg Asn Ser Arg Thr Ser Leu Phe Ser 565 570 575 Phe Arg Gly Arg Ala Lys Asp Val Gly Ser Glu Asn Asp Phe Ala Asp 580 585 590 Asp Glu His Ser Thr Phe Glu Asp Asn Glu Ser Arg Arg Asp Ser Leu 595 600 605 Phe Val Pro Arg Arg His Gly Glu Arg Arg Asn Ser Asn Leu Ser Gln 610 615 620 Thr Ser Arg Ser Ser Arg Met Leu Ala Val Phe Pro Ala Asn Gly Lys 625 630 635 640 Met His Ser Thr Val Asp Cys Asn Gly Val Val Ser Leu Val Gly Gly 645 650 655 Pro Ser Val Pro Thr Ser Pro Val Gly Gln Leu Leu Pro Glu Gly Thr 660 665 670 Thr Thr Glu Thr Glu Met Arg Lys Arg Arg Ser Ser Ser Phe His Val 675 680 685 Ser Met Asp Phe Leu Glu Asp Pro Ser Gln Arg Gln Arg Ala Met Ser 690 695 700 Ile Ala Ser Ile Leu Thr Asn Thr Val Glu Glu Leu Glu Glu Ser Arg 705 710 715 720 Gln Lys Cys Pro Pro Cys Trp Tyr Lys Phe Ser Asn Ile Phe Leu Ile 725 730 735 Trp Asp Cys Ser Pro Tyr Trp Leu Lys Val Lys His Val Val Asn Leu 740 745 750 Val Val Met Asp Pro Phe Val Asp Leu Ala Ile Thr Ile Cys Ile Val 755 760 765 Leu Asn Thr Leu Phe Met Ala Met Glu His Tyr Pro Met Thr Asp His 770 775 780 Phe Asn Asn Val Leu Thr Val Gly Asn Leu Val Phe Thr Gly Ile Phe 785 790 795 800 Thr Ala Glu Met Phe Leu Lys Ile Ile Ala Met Asp Pro Tyr Tyr Tyr 805 810 815 Phe Gln Glu Gly Trp Asn Ile Phe Asp Gly Phe Ile Val Thr Leu Ser 820 825 830 Leu Val Glu Leu Gly Leu Ala Asn Val Glu Gly Leu Ser Val Leu Arg 835 840 845 Ser Phe Arg Leu Leu Arg Val Phe Lys Leu Ala Lys Ser Trp Pro Thr 850 855 860 Leu Asn Met Leu Ile Lys Ile Ile Gly Asn Ser Val Gly Ala Leu Gly 865 870 875 880 Asn Leu Thr Leu Val Leu Ala Ile Ile Val Phe Ile Phe Ala Val Val 885 890 895 Gly Met Gln Leu Phe Gly Lys Ser Tyr Lys Asp Cys Val Cys Lys Ile 900 905 910 Ala Ser Asp Cys Gln Leu Pro Arg Trp His Met Asn Asp Phe Phe His 915 920 925 Ser Phe Leu Ile Val Phe Arg Val Leu Cys Gly Glu Trp Ile Glu Thr 930 935 940 Met Trp Asp Cys Met Glu Val Ala Gly Gln Ala Met Cys Leu Thr Val 945 950 955 960 Phe Met Met Val Met Val Ile Gly Asn Leu Val Val Leu Asn Leu Phe 965 970 975 Leu Ala Leu Leu Xaa Ser Ser Phe Ser Ala Asp Asn Leu Ala Ala Thr 980 985 990 Asp Asp Asp Asn Glu Met Asn Asn Leu Gln Ile Ala Val Asp Arg Met 995 1000 1005 His Lys Gly Val Ala Tyr Val Lys Arg Lys Ile Tyr Glu Phe Ile Gln 1010 1015 1020 Gln Ser Phe Ile Arg Lys Gln Lys Ile Leu Asp Glu Ile Lys Pro Leu 1025 1030 1035 1040 Asp Asp Leu Asn Asn Lys Lys Asp Ser Cys Met Ser Asn His Thr Xaa 1045 1050 1055 Glu Ile Gly Lys Asp Leu Asp Tyr Leu Lys Asp Val Asn Gly Thr Thr 1060 1065 1070 Ser Gly Ile Gly Thr Gly Ser Ser Val Glu Lys Tyr Ile Ile Asp Glu 1075 1080 1085 Ser Asp Tyr Met Ser Phe Ile Asn Asn Pro Ser Leu Thr Val Thr Val 1090 1095 1100 Pro Ile Ala Val Gly Glu Ser Asp Phe Glu Asn Leu Asn Thr Glu Asp 1105 1110 1115 1120 Phe Ser Ser Glu Ser Asp Leu Glu Glu Ser Lys Glu Lys Leu Asn Glu 1125 1130 1135 Ser Ser Ser Ser Ser Glu Gly Ser Thr Val Asp Ile Gly Ala Pro Val 1140 1145 1150 Glu Glu Gln Pro Val Val Glu Pro Glu Glu Thr Leu Glu Pro Glu Ala 1155 1160 1165 Cys Phe Thr Glu Gly Cys Val Gln Arg Phe Lys Cys Cys Gln Ile Asn 1170 1175 1180 Val Glu Glu Gly Arg Gly Lys Gln Trp Trp Asn Leu Arg Arg Thr Cys 1185 1190 1195 1200 Phe Arg Ile Val Glu His Asn Trp Phe Glu Thr Phe Ile Val Phe Met 1205 1210 1215 Ile Leu Leu Ser Ser Gly Ala Leu Ala Phe Glu Asp Ile Tyr Ile Asp 1220 1225 1230 Gln Arg Lys Thr Ile Lys Thr Met Leu Glu Tyr Ala Asp Lys Val Phe 1235 1240 1245 Thr Tyr Ile Phe Ile Leu Glu Met Leu Leu Lys Trp Val Ala Tyr Gly 1250 1255 1260 Tyr Gln Thr Tyr Phe Thr Asn Ala Trp Cys Trp Leu Asp Phe Leu Ile 1265 1270 1275 1280 Val Asp Val Ser Leu Val Ser Leu Thr Ala Asn Ala Leu Gly Tyr Ser 1285 1290 1295 Glu Leu Gly Ala Ile Lys Ser Leu Arg Thr Leu Arg Ala Leu Arg Pro 1300 1305 1310 Leu Arg Ala Leu Ser Arg Phe Glu Gly Met Arg Val Val Val Asn Ala 1315 1320 1325 Leu Leu Gly Ala Ile Pro Ser Ile Met Asn Val Leu Leu Val Cys Leu 1330 1335 1340 Ile Phe Trp Leu Ile Phe Ser Ile Met Gly Val Asn Leu Phe Ala Gly 1345 1350 1355 1360 Lys Phe Tyr His Cys Ile Asn Thr Thr Thr Gly Asp Arg Phe Asp Ile 1365 1370 1375 Glu Asp Val Asn Asn His Thr Asp Cys Leu Lys Leu Ile Glu Arg Asn 1380 1385 1390 Glu Thr Ala Arg Trp Lys Asn Val Lys Val Asn Phe Asp Asn Val Gly 1395 1400 1405 Phe Gly Tyr Leu Ser Leu Leu Gln Val Ala Thr Phe Lys Gly Trp Met 1410 1415 1420 Asp Ile Met Tyr Ala Ala Val Asp Ser Arg Asn Val Glu Leu Gln Pro 1425 1430 1435 1440 Lys Tyr Glu Glu Ser Leu Tyr Met Tyr Leu Tyr Phe Val Ile Phe Ile 1445 1450 1455 Ile Phe Gly Ser Phe Phe Thr Leu Asn Leu Phe Ile Gly Val Ile Ile 1460 1465 1470 Asp Asn Phe Asn Gln Gln Lys Lys Lys Phe Gly Gly Gln Asp Ile Phe 1475 1480 1485 Met Thr Glu Glu Gln Lys Lys Tyr Tyr Asn Ala Met Lys Lys Leu Gly 1490 1495 1500 Ser Lys Lys Pro Gln Lys Pro Ile Pro Arg Pro Gly Asn Lys Phe Gln 1505 1510 1515 1520 Gly Met Val Phe Asp Phe Val Thr Arg Gln Val Phe Asp Ile Ser Ile 1525 1530 1535 Met Ile Leu Ile Cys Leu Asn Met Val Thr Met Met Val Glu Thr Asp 1540 1545 1550 Asp Gln Ser Glu Tyr Val Thr Thr Ile Leu Ser Arg Ile Asn Leu Val 1555 1560 1565 Phe Ile Val Leu Phe Thr Gly Glu Cys Val Leu Lys Leu Ile Ser Leu 1570 1575 1580 Arg His Tyr Tyr Phe Thr Ile Gly Trp Asn Ile Phe Asp Phe Val Val 1585 1590 1595 1600 Val Ile Leu Ser Ile Val Gly Met Phe Leu Ala Glu Leu Ile Glu Lys 1605 1610 1615 Tyr Phe Val Ser Pro Thr Leu Phe Arg Val Ile Arg Leu Ala Arg Ile 1620 1625 1630 Gly Arg Ile Leu Arg Leu Ile Lys Gly Ala Lys Gly Ile Arg Thr Leu 1635 1640 1645 Leu Phe Ala Leu Met Met Ser Leu Pro Ala Leu Phe Asn Ile Gly Leu 1650 1655 1660 Leu Leu Phe Leu Val Met Phe Ile Tyr Ala Ile Phe Gly Met Ser Asn 1665 1670 1675 1680 Phe Ala Tyr Val Lys Arg Glu Val Gly Ile Asp Asp Met Phe Asn Phe 1685 1690 1695 Glu Thr Phe Gly Asn Ser Met Ile Cys Leu Phe Gln Ile Thr Thr Ser 1700 1705 1710 Ala Gly Trp Asp Gly Leu Leu Ala Pro Ile Leu Asn Ser Lys Pro Pro 1715 1720 1725 Asp Cys Asp Pro Asn Lys Val Asn Pro Gly Ser Ser Val Lys Gly Asp 1730 1735 1740 Cys Gly Asn Pro Ser Val Gly Ile Phe Phe Phe Val Ser Tyr Ile Ile 1745 1750 1755 1760 Ile Ser Phe Leu Val Val Val Asn Met Tyr Ile Ala Val Ile Leu Glu 1765 1770 1775 Asn Phe Ser Val Ala Thr Glu Glu Ser Ala Glu Pro Leu Ser Glu Asp 1780 1785 1790 Asp Phe Glu Met Phe Tyr Glu Val Trp Glu Lys Phe Asp Pro Asp Ala 1795 1800 1805 Thr Gln Phe Met Glu Phe Glu Lys Leu Ser Gln Phe Ala Ala Ala Leu 1810 1815 1820 Glu Pro Pro Leu Asn Leu Pro Gln Pro Asn Lys Leu Gln Leu Ile Ala 1825 1830 1835 1840 Met Asp Leu Pro Met Val Ser Gly Asp Arg Ile His Cys Leu Asp Ile 1845 1850 1855 Leu Phe Ala Phe Thr Lys Arg Val Leu Gly Glu Ser Gly Glu Met Asp 1860 1865 1870 Ala Leu Arg Ile Gln Met Glu Glu Arg Phe Met Ala Ser Asn Pro Ser 1875 1880 1885 Lys Val Ser Tyr Gln Pro Ile Thr Thr Thr Leu Lys Arg Lys Gln Glu 1890 1895 1900 Glu Val Ser Ala Val Ile Ile Gln Arg Ala Tyr Arg Arg His Leu Leu 1905 1910 1915 1920 Lys Arg Thr Val Lys Gln Ala Ser Phe Thr Tyr Asn Lys Asn Lys Ile 1925 1930 1935 Lys Gly Gly Ala Asn Leu Leu Ile Lys Glu Asp Met Ile Ile Asp Arg 1940 1945 1950 Ile Asn Glu Asn Ser Ile Thr Glu Lys Thr Asp Leu Thr Met Ser Thr 1955 1960 1965 Ala Ala Cys Pro Pro Ser Tyr Asp Arg Val Thr Lys Pro Ile Val Glu 1970 1975 1980 Lys His Glu Gln Glu Gly Lys Asp Glu Lys Ala Lys Gly Lys 1985 1990 1995 3 5889 DNA homo sapiens 3 atggagcaaa cagtgcttgt accaccagga cctgacagct tcaacttctt caccagagaa 60 tctcttgcgg ctattgaaag acgcattgca gaagaaaagg caaagaatcc caaaccagac 120 aaaaaagatg acgacgaaaa tggcccaaag ccaaatagtg acttggaagc tggaaagaac 180 cttccattta tttatggaga cattcctcca gagatggtgt cagagcccct ggaggacctg 240 gacccctact atatcaataa gaaaactttt atagtattga ataaagggaa ggccatcttc 300 cggttcagtg ccacctctgc cctgtacatt ttaactccct tcaatcctct taggaaaata 360 gctattaaga ttttggtaca ttcattattc agcatgctaa ttatgtgcac tattttgaca 420 aactgtgtgt ttatgacaat gagtaaccct cctgattgga caaagaatgt agaatacacc 480 ttcacaggaa tatatacttt tgaatcactt ataaaaatta ttgcaagggg attctgttta 540 gaagatttta ctttccttcg ggatccatgg aactggctcg atttcactgt cattacattt 600 gcgtacgtca cagagtttgt ggacctgggc aatgtctcgg cattgagaac attcagagtt 660 ctccgagcat tgaagacgat ttcagtcatt ccaggcctga aaaccattgt gggagccctg 720 atccagtctg tgaagaagct ctcagatgta atgatcctga ctgtgttctg tctgagcgta 780 tttgctctaa ttgggctgca gctgttcatg ggcaacctga ggaataaatg tatacaatgg 840 cctcccacca atgcttcctt ggaggaacat agtatagaaa agaatataac tgtgaattat 900 aatggtacac ttataaatga aactgtcttt gagtttgact ggaagtcata tattcaagat 960 tcaagatatc attatttcct ggagggtttt ttagatgcac tactatgtgg aaatagctct 1020 gatgcaggcc aatgtccaga gggatatatg tgtgtgaaag ctggtagaaa tcccaattat 1080 ggctacacaa gctttgatac cttcagttgg gcttttttgt ccttgtttcg actaatgact 1140 caggacttct gggaaaatct ttatcaactg acattacgtg ctgctgggaa aacgtacatg 1200 atattttttg tgttggtcat tttcttgggc tcattctacc taataaattt gatcctggct 1260 gtggtggcca tggcctacga ggaacagaat caggccacct tggaagaagc agaacagaaa 1320 gaggccgaat ttcagcagat gattgaacag cttaaaaagc aacaggaggc agctcagcag 1380 gcagcaacgg caactgcctc agaacattcc agagagccca gtgcagcagg caggctctca 1440 gacagctcat ctgaagcctc taagttgagt tccaagagtg ctaaggaaag aagaaatcgg 1500 aggaagaaaa gaaaacagaa agagcagtct ggtggggaag agaaagatga ggatgaattc 1560 caaaaatctg aatctgagga cagcatcagg aggaaaggtt ttcgcttctc cattgaaggg 1620 aaccgattga catatgaaaa gaggtactcc tccccacacc agtctttgtt gagcatccgt 1680 ggctccctat tttcaccaag gcgaaatagc agaacaagcc ttttcagctt tagagggcga 1740 gcaaaggatg tgggatctga gaacgacttc gcagatgatg agcacagcac ctttgaggat 1800 aacgagagcc gtagagattc cttgtttgtg ccccgacgac acggagagag acgcaacagc 1860 aacctgagtc agaccagtag gtcatcccgg atgctggcag tgtttccagc gaatgggaag 1920 atgcacagca ctgtggattg caatggtgtg gtttccttgg ttggtggacc ttcagttcct 1980 acatcgcctg ttggacagct tctgccagag ggaacaacca ctgaaactga aatgagaaag 2040 agaaggtcaa gttctttcca cgtttccatg gactttctag aagatccttc ccaaaggcaa 2100 cgagcaatga gtatagccag cattctaaca aatacagtag aagaacttga agaatccagg 2160 cagaaatgcc caccctgttg gtataaattt tccaacatat tcttaatctg ggactgttct 2220 ccatattggt taaaagtgaa acatgttgtc aacctggtyg tgatggaccc atttgttgac 2280 ctggccatca ccatctgtat tgtcttaaat actcttttca tggccatgga gcactatcca 2340 atgacggacc atttcaataa tgtgcttaca gtaggaaact tggttttcac tgggatcttt 2400 acagcagaaa tgtttctgaa aattattgcc atggatcctt actattattt ccaagaaggc 2460 tggaatatct ttgacggttt tattgtgacg cttagcctgg tagaacttgg actcgccaat 2520 gtggaaggat tatctgttct ccgttcattt cgattgctgc gagttttcaa gttggcaaaa 2580 tcttggccaa cgttaaatat gctaataaag atcatcggca attccgtggg ggctctggga 2640 aatttaaccc tcgtcttggc catcatcgtc ttcatttttg ccgtggtcgg catgcagctc 2700 tttggtaaaa gctacaaaga ttgtgtctgc aagatcgcca gtgattgtca actcccacgc 2760 tggcacatga atgacttctt ccactccttc ctgattgtgt tccgcgtgct gtgtggggag 2820 tggatagaga ccatgtggga ctgtatggag gttgctggtc aagccatgtg ccttactgtc 2880 ttcatgatgg tcatggtgat tggaaaccta gtggtcctga atctctttct ggccttgctt 2940 mtgagctcat ttagtgcaga caaccttgca gccactgatg atgataatga aatgaataat 3000 ctccaaattg ctgtggatag gatgcacaaa ggagtagctt atgtgaaaag aaaaatatat 3060 gaatttattc aacagtcctt cattaggaaa caaaagattt tagatgaaat taaaccactt 3120 gatgatctaa acaacaagaa agacagttgt atgtccaatc atacarcaga aattgggaaa 3180 gatcttgact atcttaaaga tgtaaatgga actacaagtg gtataggaac tggcagcagt 3240 gttgaaaaat acattattga tgaaagtgat tacatgtcat tcataaacaa ccccagtctt 3300 actgtgactg taccaattgc tgtaggagaa tctgactttg aaaatttaaa cacggaagac 3360 tttagtagtg aatcggatct ggaagaaagc aaagagaaac tgaatgaaag cagtagctca 3420 tcagaaggta gcactgtgga catcggcgca cctgtagaag aacagcccgt agtggaacct 3480 gaagaaactc ttgaaccaga agcttgtttc actgaaggct gtgtacaaag attcaagtgt 3540 tgtcaaatca atgtggaaga aggcagagga aaacaatggt ggaacctgag aaggacgtgt 3600 ttccgaatag ttgaacataa ctggtttgag accttcattg ttttcatgat tctccttagt 3660 agtggtgctc tggcatttga agatatatat attgatcagc gaaagacgat taagacgatg 3720 ttggaatatg ctgacaaggt tttcacttac attttcattc tggaaatgct tctaaaatgg 3780 gtggcatatg gctatcaaac atatttcacc aatgcctggt gttggctgga cttcttaatt 3840 gttgatgttt cattggtcag tttaacagca aatgccttgg gttactcaga acttggagcc 3900 atcaaatctc tcaggacact aagagctctg agacctctaa gagccttatc tcgatttgaa 3960 gggatgaggg tggttgtgaa tgccctttta ggagcaattc catccatcat gaatgtgctt 4020 ctggtttgtc ttatattctg gctaattttc agcatcatgg gcgtaaattt gtttgctggc 4080 aaattctacc actgtattaa caccacaact ggtgacaggt ttgacatcga agacgtgaat 4140 aatcatactg attgcctaaa actaatagaa agaaatgaga ctgctcgatg gaaaaatgtg 4200 aaagtaaact ttgataatgt aggatttggg tatctctctt tgcttcaagt tgccacattc 4260 aaaggatgga tggatataat gtatgcagca gttgattcca gaaatgtgga actccagcct 4320 aagtatgaag aaagtctgta catgtatctt tactttgtta ttttcatcat ctttgggtcc 4380 ttcttcacct tgaacctgtt tattggtgtc atcatagata atttcaacca gcagaaaaag 4440 aagtttggag gtcaagacat ctttatgaca gaagaacaga agaaatacta taatgcaatg 4500 aaaaaattag gatcgaaaaa accgcaaaag cctatacctc gaccaggaaa caaatttcaa 4560 ggaatggtct ttgacttcgt aaccagacaa gtttttgaca taagcatcat gattctcatc 4620 tgtcttaaca tggtcacaat gatggtggaa acagatgacc agagtgaata tgtgactacc 4680 attttgtcac gcatcaatct ggtgttcatt gtgctattta ctggagagtg tgtactgaaa 4740 ctcatctctc tacgccatta ttattttacc attggatgga atatttttga ttttgtggtt 4800 gtcattctct ccattgtagg tatgtttctt gccgagctga tagaaaagta tttcgtgtcc 4860 cctaccctgt tccgagtgat ccgtcttgct aggattggcc gaatcctacg tctgatcaaa 4920 ggagcaaagg ggatccgcac gctgctcttt gctttgatga tgtcccttcc tgcgttgttt 4980 aacatcggcc tcctactctt cctagtcatg ttcatctacg ccatctttgg gatgtccaac 5040 tttgcctatg ttaagaggga agttgggatc gatgacatgt tcaactttga gacctttggc 5100 aacagcatga tctgcctatt ccaaattaca acctctgctg gctgggatgg attgctagca 5160 cccattctca acagtaagcc acccgactgt gaccctaata aagttaaccc tggaagctca 5220 gttaagggag actgtgggaa cccatctgtt ggaattttct tttttgtcag ttacatcatc 5280 atatccttcc tggttgtggt gaacatgtac atcgcggtca tcctggagaa cttcagtgtt 5340 gctactgaag aaagtgcaga gcctctgagt gaggatgact ttgagatgtt ctatgaggtt 5400 tgggagaagt ttgatcccga tgcaactcag ttcatggaat ttgaaaaatt atctcagttt 5460 gcagctgcgc ttgaaccgcc tctcaatctg ccacaaccaa acaaactcca gctcattgcc 5520 atggatttgc ccatggtgag tggtgaccgg atccactgtc ttgatatctt atttgctttt 5580 acaaagcggg ttctaggaga gagtggagag atggatgctc tacgaataca gatggaagag 5640 cgattcatgg cttccaatcc ttccaaggtc tcctatcagc caatcactac tactttaaaa 5700 cgaaaacaag aggaagtatc tgctgtcatt attcagcgtg cttacagacg ccacctttta 5760 aagcgaactg taaaacaagc ttcctttacg tacaataaaa acaaaatcaa aggtggggct 5820 aatcttctta taaaagaaga catgataatt gacagaataa atgaaaactc tattacagaa 5880 aaaaactga 5889 4 1962 PRT homo sapiens VARIANT (1)...(1962) Xaa = Any Amino Acid 4 Met Glu Gln Thr Val Leu Val Pro Pro Gly Pro Asp Ser Phe Asn Phe 1 5 10 15 Phe Thr Arg Glu Ser Leu Ala Ala Ile Glu Arg Arg Ile Ala Glu Glu 20 25 30 Lys Ala Lys Asn Pro Lys Pro Asp Lys Lys Asp Asp Asp Glu Asn Gly 35 40 45 Pro Lys Pro Asn Ser Asp Leu Glu Ala Gly Lys Asn Leu Pro Phe Ile 50 55 60 Tyr Gly Asp Ile Pro Pro Glu Met Val Ser Glu Pro Leu Glu Asp Leu 65 70 75 80 Asp Pro Tyr Tyr Ile Asn Lys Lys Thr Phe Ile Val Leu Asn Lys Gly 85 90 95 Lys Ala Ile Phe Arg Phe Ser Ala Thr Ser Ala Leu Tyr Ile Leu Thr 100 105 110 Pro Phe Asn Pro Leu Arg Lys Ile Ala Ile Lys Ile Leu Val His Ser 115 120 125 Leu Phe Ser Met Leu Ile Met Cys Thr Ile Leu Thr Asn Cys Val Phe 130 135 140 Met Thr Met Ser Asn Pro Pro Asp Trp Thr Lys Asn Val Glu Tyr Thr 145 150 155 160 Phe Thr Gly Ile Tyr Thr Phe Glu Ser Leu Ile Lys Ile Ile Ala Arg 165 170 175 Gly Phe Cys Leu Glu Asp Phe Thr Phe Leu Arg Asp Pro Trp Asn Trp 180 185 190 Leu Asp Phe Thr Val Ile Thr Phe Ala Tyr Val Thr Glu Phe Val Asp 195 200 205 Leu Gly Asn Val Ser Ala Leu Arg Thr Phe Arg Val Leu Arg Ala Leu 210 215 220 Lys Thr Ile Ser Val Ile Pro Gly Leu Lys Thr Ile Val Gly Ala Leu 225 230 235 240 Ile Gln Ser Val Lys Lys Leu Ser Asp Val Met Ile Leu Thr Val Phe 245 250 255 Cys Leu Ser Val Phe Ala Leu Ile Gly Leu Gln Leu Phe Met Gly Asn 260 265 270 Leu Arg Asn Lys Cys Ile Gln Trp Pro Pro Thr Asn Ala Ser Leu Glu 275 280 285 Glu His Ser Ile Glu Lys Asn Ile Thr Val Asn Tyr Asn Gly Thr Leu 290 295 300 Ile Asn Glu Thr Val Phe Glu Phe Asp Trp Lys Ser Tyr Ile Gln Asp 305 310 315 320 Ser Arg Tyr His Tyr Phe Leu Glu Gly Phe Leu Asp Ala Leu Leu Cys 325 330 335 Gly Asn Ser Ser Asp Ala Gly Gln Cys Pro Glu Gly Tyr Met Cys Val 340 345 350 Lys Ala Gly Arg Asn Pro Asn Tyr Gly Tyr Thr Ser Phe Asp Thr Phe 355 360 365 Ser Trp Ala Phe Leu Ser Leu Phe Arg Leu Met Thr Gln Asp Phe Trp 370 375 380 Glu Asn Leu Tyr Gln Leu Thr Leu Arg Ala Ala Gly Lys Thr Tyr Met 385 390 395 400 Ile Phe Phe Val Leu Val Ile Phe Leu Gly Ser Phe Tyr Leu Ile Asn 405 410 415 Leu Ile Leu Ala Val Val Ala Met Ala Tyr Glu Glu Gln Asn Gln Ala 420 425 430 Thr Leu Glu Glu Ala Glu Gln Lys Glu Ala Glu Phe Gln Gln Met Ile 435 440 445 Glu Gln Leu Lys Lys Gln Gln Glu Ala Ala Gln Gln Ala Ala Thr Ala 450 455 460 Thr Ala Ser Glu His Ser Arg Glu Pro Ser Ala Ala Gly Arg Leu Ser 465 470 475 480 Asp Ser Ser Ser Glu Ala Ser Lys Leu Ser Ser Lys Ser Ala Lys Glu 485 490 495 Arg Arg Asn Arg Arg Lys Lys Arg Lys Gln Lys Glu Gln Ser Gly Gly 500 505 510 Glu Glu Lys Asp Glu Asp Glu Phe Gln Lys Ser Glu Ser Glu Asp Ser 515 520 525 Ile Arg Arg Lys Gly Phe Arg Phe Ser Ile Glu Gly Asn Arg Leu Thr 530 535 540 Tyr Glu Lys Arg Tyr Ser Ser Pro His Gln Ser Leu Leu Ser Ile Arg 545 550 555 560 Gly Ser Leu Phe Ser Pro Arg Arg Asn Ser Arg Thr Ser Leu Phe Ser 565 570 575 Phe Arg Gly Arg Ala Lys Asp Val Gly Ser Glu Asn Asp Phe Ala Asp 580 585 590 Asp Glu His Ser Thr Phe Glu Asp Asn Glu Ser Arg Arg Asp Ser Leu 595 600 605 Phe Val Pro Arg Arg His Gly Glu Arg Arg Asn Ser Asn Leu Ser Gln 610 615 620 Thr Ser Arg Ser Ser Arg Met Leu Ala Val Phe Pro Ala Asn Gly Lys 625 630 635 640 Met His Ser Thr Val Asp Cys Asn Gly Val Val Ser Leu Val Gly Gly 645 650 655 Pro Ser Val Pro Thr Ser Pro Val Gly Gln Leu Leu Pro Glu Gly Thr 660 665 670 Thr Thr Glu Thr Glu Met Arg Lys Arg Arg Ser Ser Ser Phe His Val 675 680 685 Ser Met Asp Phe Leu Glu Asp Pro Ser Gln Arg Gln Arg Ala Met Ser 690 695 700 Ile Ala Ser Ile Leu Thr Asn Thr Val Glu Glu Leu Glu Glu Ser Arg 705 710 715 720 Gln Lys Cys Pro Pro Cys Trp Tyr Lys Phe Ser Asn Ile Phe Leu Ile 725 730 735 Trp Asp Cys Ser Pro Tyr Trp Leu Lys Val Lys His Val Val Asn Leu 740 745 750 Val Val Met Asp Pro Phe Val Asp Leu Ala Ile Thr Ile Cys Ile Val 755 760 765 Leu Asn Thr Leu Phe Met Ala Met Glu His Tyr Pro Met Thr Asp His 770 775 780 Phe Asn Asn Val Leu Thr Val Gly Asn Leu Val Phe Thr Gly Ile Phe 785 790 795 800 Thr Ala Glu Met Phe Leu Lys Ile Ile Ala Met Asp Pro Tyr Tyr Tyr 805 810 815 Phe Gln Glu Gly Trp Asn Ile Phe Asp Gly Phe Ile Val Thr Leu Ser 820 825 830 Leu Val Glu Leu Gly Leu Ala Asn Val Glu Gly Leu Ser Val Leu Arg 835 840 845 Ser Phe Arg Leu Leu Arg Val Phe Lys Leu Ala Lys Ser Trp Pro Thr 850 855 860 Leu Asn Met Leu Ile Lys Ile Ile Gly Asn Ser Val Gly Ala Leu Gly 865 870 875 880 Asn Leu Thr Leu Val Leu Ala Ile Ile Val Phe Ile Phe Ala Val Val 885 890 895 Gly Met Gln Leu Phe Gly Lys Ser Tyr Lys Asp Cys Val Cys Lys Ile 900 905 910 Ala Ser Asp Cys Gln Leu Pro Arg Trp His Met Asn Asp Phe Phe His 915 920 925 Ser Phe Leu Ile Val Phe Arg Val Leu Cys Gly Glu Trp Ile Glu Thr 930 935 940 Met Trp Asp Cys Met Glu Val Ala Gly Gln Ala Met Cys Leu Thr Val 945 950 955 960 Phe Met Met Val Met Val Ile Gly Asn Leu Val Val Leu Asn Leu Phe 965 970 975 Leu Ala Leu Leu Xaa Ser Ser Phe Ser Ala Asp Asn Leu Ala Ala Thr 980 985 990 Asp Asp Asp Asn Glu Met Asn Asn Leu Gln Ile Ala Val Asp Arg Met 995 1000 1005 His Lys Gly Val Ala Tyr Val Lys Arg Lys Ile Tyr Glu Phe Ile Gln 1010 1015 1020 Gln Ser Phe Ile Arg Lys Gln Lys Ile Leu Asp Glu Ile Lys Pro Leu 1025 1030 1035 1040 Asp Asp Leu Asn Asn Lys Lys Asp Ser Cys Met Ser Asn His Thr Xaa 1045 1050 1055 Glu Ile Gly Lys Asp Leu Asp Tyr Leu Lys Asp Val Asn Gly Thr Thr 1060 1065 1070 Ser Gly Ile Gly Thr Gly Ser Ser Val Glu Lys Tyr Ile Ile Asp Glu 1075 1080 1085 Ser Asp Tyr Met Ser Phe Ile Asn Asn Pro Ser Leu Thr Val Thr Val 1090 1095 1100 Pro Ile Ala Val Gly Glu Ser Asp Phe Glu Asn Leu Asn Thr Glu Asp 1105 1110 1115 1120 Phe Ser Ser Glu Ser Asp Leu Glu Glu Ser Lys Glu Lys Leu Asn Glu 1125 1130 1135 Ser Ser Ser Ser Ser Glu Gly Ser Thr Val Asp Ile Gly Ala Pro Val 1140 1145 1150 Glu Glu Gln Pro Val Val Glu Pro Glu Glu Thr Leu Glu Pro Glu Ala 1155 1160 1165 Cys Phe Thr Glu Gly Cys Val Gln Arg Phe Lys Cys Cys Gln Ile Asn 1170 1175 1180 Val Glu Glu Gly Arg Gly Lys Gln Trp Trp Asn Leu Arg Arg Thr Cys 1185 1190 1195 1200 Phe Arg Ile Val Glu His Asn Trp Phe Glu Thr Phe Ile Val Phe Met 1205 1210 1215 Ile Leu Leu Ser Ser Gly Ala Leu Ala Phe Glu Asp Ile Tyr Ile Asp 1220 1225 1230 Gln Arg Lys Thr Ile Lys Thr Met Leu Glu Tyr Ala Asp Lys Val Phe 1235 1240 1245 Thr Tyr Ile Phe Ile Leu Glu Met Leu Leu Lys Trp Val Ala Tyr Gly 1250 1255 1260 Tyr Gln Thr Tyr Phe Thr Asn Ala Trp Cys Trp Leu Asp Phe Leu Ile 1265 1270 1275 1280 Val Asp Val Ser Leu Val Ser Leu Thr Ala Asn Ala Leu Gly Tyr Ser 1285 1290 1295 Glu Leu Gly Ala Ile Lys Ser Leu Arg Thr Leu Arg Ala Leu Arg Pro 1300 1305 1310 Leu Arg Ala Leu Ser Arg Phe Glu Gly Met Arg Val Val Val Asn Ala 1315 1320 1325 Leu Leu Gly Ala Ile Pro Ser Ile Met Asn Val Leu Leu Val Cys Leu 1330 1335 1340 Ile Phe Trp Leu Ile Phe Ser Ile Met Gly Val Asn Leu Phe Ala Gly 1345 1350 1355 1360 Lys Phe Tyr His Cys Ile Asn Thr Thr Thr Gly Asp Arg Phe Asp Ile 1365 1370 1375 Glu Asp Val Asn Asn His Thr Asp Cys Leu Lys Leu Ile Glu Arg Asn 1380 1385 1390 Glu Thr Ala Arg Trp Lys Asn Val Lys Val Asn Phe Asp Asn Val Gly 1395 1400 1405 Phe Gly Tyr Leu Ser Leu Leu Gln Val Ala Thr Phe Lys Gly Trp Met 1410 1415 1420 Asp Ile Met Tyr Ala Ala Val Asp Ser Arg Asn Val Glu Leu Gln Pro 1425 1430 1435 1440 Lys Tyr Glu Glu Ser Leu Tyr Met Tyr Leu Tyr Phe Val Ile Phe Ile 1445 1450 1455 Ile Phe Gly Ser Phe Phe Thr Leu Asn Leu Phe Ile Gly Val Ile Ile 1460 1465 1470 Asp Asn Phe Asn Gln Gln Lys Lys Lys Phe Gly Gly Gln Asp Ile Phe 1475 1480 1485 Met Thr Glu Glu Gln Lys Lys Tyr Tyr Asn Ala Met Lys Lys Leu Gly 1490 1495 1500 Ser Lys Lys Pro Gln Lys Pro Ile Pro Arg Pro Gly Asn Lys Phe Gln 1505 1510 1515 1520 Gly Met Val Phe Asp Phe Val Thr Arg Gln Val Phe Asp Ile Ser Ile 1525 1530 1535 Met Ile Leu Ile Cys Leu Asn Met Val Thr Met Met Val Glu Thr Asp 1540 1545 1550 Asp Gln Ser Glu Tyr Val Thr Thr Ile Leu Ser Arg Ile Asn Leu Val 1555 1560 1565 Phe Ile Val Leu Phe Thr Gly Glu Cys Val Leu Lys Leu Ile Ser Leu 1570 1575 1580 Arg His Tyr Tyr Phe Thr Ile Gly Trp Asn Ile Phe Asp Phe Val Val 1585 1590 1595 1600 Val Ile Leu Ser Ile Val Gly Met Phe Leu Ala Glu Leu Ile Glu Lys 1605 1610 1615 Tyr Phe Val Ser Pro Thr Leu Phe Arg Val Ile Arg Leu Ala Arg Ile 1620 1625 1630 Gly Arg Ile Leu Arg Leu Ile Lys Gly Ala Lys Gly Ile Arg Thr Leu 1635 1640 1645 Leu Phe Ala Leu Met Met Ser Leu Pro Ala Leu Phe Asn Ile Gly Leu 1650 1655 1660 Leu Leu Phe Leu Val Met Phe Ile Tyr Ala Ile Phe Gly Met Ser Asn 1665 1670 1675 1680 Phe Ala Tyr Val Lys Arg Glu Val Gly Ile Asp Asp Met Phe Asn Phe 1685 1690 1695 Glu Thr Phe Gly Asn Ser Met Ile Cys Leu Phe Gln Ile Thr Thr Ser 1700 1705 1710 Ala Gly Trp Asp Gly Leu Leu Ala Pro Ile Leu Asn Ser Lys Pro Pro 1715 1720 1725 Asp Cys Asp Pro Asn Lys Val Asn Pro Gly Ser Ser Val Lys Gly Asp 1730 1735 1740 Cys Gly Asn Pro Ser Val Gly Ile Phe Phe Phe Val Ser Tyr Ile Ile 1745 1750 1755 1760 Ile Ser Phe Leu Val Val Val Asn Met Tyr Ile Ala Val Ile Leu Glu 1765 1770 1775 Asn Phe Ser Val Ala Thr Glu Glu Ser Ala Glu Pro Leu Ser Glu Asp 1780 1785 1790 Asp Phe Glu Met Phe Tyr Glu Val Trp Glu Lys Phe Asp Pro Asp Ala 1795 1800 1805 Thr Gln Phe Met Glu Phe Glu Lys Leu Ser Gln Phe Ala Ala Ala Leu 1810 1815 1820 Glu Pro Pro Leu Asn Leu Pro Gln Pro Asn Lys Leu Gln Leu Ile Ala 1825 1830 1835 1840 Met Asp Leu Pro Met Val Ser Gly Asp Arg Ile His Cys Leu Asp Ile 1845 1850 1855 Leu Phe Ala Phe Thr Lys Arg Val Leu Gly Glu Ser Gly Glu Met Asp 1860 1865 1870 Ala Leu Arg Ile Gln Met Glu Glu Arg Phe Met Ala Ser Asn Pro Ser 1875 1880 1885 Lys Val Ser Tyr Gln Pro Ile Thr Thr Thr Leu Lys Arg Lys Gln Glu 1890 1895 1900 Glu Val Ser Ala Val Ile Ile Gln Arg Ala Tyr Arg Arg His Leu Leu 1905 1910 1915 1920 Lys Arg Thr Val Lys Gln Ala Ser Phe Thr Tyr Asn Lys Asn Lys Ile 1925 1930 1935 Lys Gly Gly Ala Asn Leu Leu Ile Lys Glu Asp Met Ile Ile Asp Arg 1940 1945 1950 Ile Asn Glu Asn Ser Ile Thr Glu Lys Asn 1955 1960 5 4329 DNA homo sapiens 5 atggagcaaa cagtgcttgt accaccagga cctgacagct tcaacttctt caccagagaa 60 tctcttgcgg ctattgaaag acgcattgca gaagaaaagg caaagaatcc caaaccagac 120 aaaaaagatg acgacgaaaa tggcccaaag ccaaatagtg acttggaagc tggaaagaac 180 cttccattta tttatggaga cattcctcca gagatggtgt cagagcccct ggaggacctg 240 gacccctact atatcaataa gaaaactttt atagtattga ataaagggaa ggccatcttc 300 cggttcagtg ccacctctgc cctgtacatt ttaactccct tcaatcctct taggaaaata 360 gctattaaga ttttggtaca ttcattattc agcatgctaa ttatgtgcac tattttgaca 420 aactgtgtgt ttatgacaat gagtaaccct cctgattgga caaagaatgt agaatacacc 480 ttcacaggaa tatatacttt tgaatcactt ataaaaatta ttgcaagggg attctgttta 540 gaagatttta ctttccttcg ggatccatgg aactggctcg atttcactgt cattacattt 600 gcgtacgtca cagagtttgt ggacctgggc aatgtctcgg cattgagaac attcagagtt 660 ctccgagcat tgaagacgat ttcagtcatt ccaggcctga aaaccattgt gggagccctg 720 atccagtctg tgaagaagct ctcagatgta atgatcctga ctgtgttctg tctgagcgta 780 tttgctctaa ttgggctgca gctgttcatg ggcaacctga ggaataaatg tatacaatgg 840 cctcccacca atgcttcctt ggaggaacat agtatagaaa agaatataac tgtgaattat 900 aatggtacac ttataaatga aactgtcttt gagtttgact ggaagtcata tattcaagat 960 tcaagatatc attatttcct ggagggtttt ttagatgcac tactatgtgg aaatagctct 1020 gatgcaggcc aatgtccaga gggatatatg tgtgtgaaag ctggtagaaa tcccaattat 1080 ggctacacaa gctttgatac cttcagttgg gcttttttgt ccttgtttcg actaatgact 1140 caggacttct gggaaaatct ttatcaactg acattacgtg ctgctgggaa aacgtacatg 1200 atattttttg tgttggtcat tttcttgggc tcattctacc taataaattt gatcctggct 1260 gtggtggcca tggcctacga ggaacagaat caggccacct tggaagaagc agaacagaaa 1320 gaggccgaat ttcagcagat gattgaacag cttaaaaagc aacaggaggc agctcagcag 1380 gcagcaacgg caactgcctc agaacattcc agagagccca gtgcagcagg caggctctca 1440 gacagctcat ctgaagcctc taagttgagt tccaagagtg ctaaggaaag aagaaatcgg 1500 aggaagaaaa gaaaacagaa agagcagtct ggtggggaag agaaagatga ggatgaattc 1560 caaaaatctg aatctgagga cagcatcagg aggaaaggtt ttcgcttctc cattgaaggg 1620 aaccgattga catatgaaaa gaggtactcc tccccacacc agtctttgtt gagcatccgt 1680 ggctccctat tttcaccaag gcgaaatagc agaacaagcc ttttcagctt tagagggcga 1740 gcaaaggatg tgggatctga gaacgacttc gcagatgatg agcacagcac ctttgaggat 1800 aacgagagcc gtagagattc cttgtttgtg ccccgacgac acggagagag acgcaacagc 1860 aacctgagtc agaccagtag gtcatcccgg atgctggcag tgtttccagc gaatgggaag 1920 atgcacagca ctgtggattg caatggtgtg gtttccttgg ttggtggacc ttcagttcct 1980 acatcgcctg ttggacagct tctgccagag ggaacaacca ctgaaactga aatgagaaag 2040 agaaggtcaa gttctttcca cgtttccatg gactttctag aagatccttc ccaaaggcaa 2100 cgagcaatga gtatagccag cattctaaca aatacagtag aagaacttga agaatccagg 2160 cagaaatgcc caccctgttg gtataaattt tccaacatat tcttaatctg ggactgttct 2220 ccatattggt taaaagtgaa acatgttgtc aacctggtyg tgatggaccc atttgttgac 2280 ctggccatca ccatctgtat tgtcttaaat actcttttca tggccatgga gcactatcca 2340 atgacggacc atttcaataa tgtgcttaca gtaggaaact tggttttcac tgggatcttt 2400 acagcagaaa tgtttctgaa aattattgcc atggatcctt actattattt ccaagaaggc 2460 tggaatatct ttgacggttt tattgtgacg cttagcctgg tagaacttgg actcgccaat 2520 gtggaaggat tatctgttct ccgttcattt cgattgctgc gagttttcaa gttggcaaaa 2580 tcttggccaa cgttaaatat gctaataaag atcatcggca attccgtggg ggctctggga 2640 aatttaaccc tcgtcttggc catcatcgtc ttcatttttg ccgtggtcgg catgcagctc 2700 tttggtaaaa gctacaaaga ttgtgtctgc aagatcgcca gtgattgtca actcccacgc 2760 tggcacatga atgacttctt ccactccttc ctgattgtgt tccgcgtgct gtgtggggag 2820 tggatagaga ccatgtggga ctgtatggag gttgctggtc aagccatgtg ccttactgtc 2880 ttcatgatgg tcatggtgat tggaaaccta gtggtcctga atctctttct ggccttgctt 2940 mtgagctcat ttagtgcaga caaccttgca gccactgatg atgataatga aatgaataat 3000 ctccaaattg ctgtggatag gatgcacaaa ggagtagctt atgtgaaaag aaaaatatat 3060 gaatttattc aacagtcctt cattaggaaa caaaagattt tagatgaaat taaaccactt 3120 gatgatctaa acaacaagaa agacagttgt atgtccaatc atacarcaga aattgggaaa 3180 gatcttgact atcttaaaga tgtaaatgga actacaagtg gtataggaac tggcagcagt 3240 gttgaaaaat acattattga tgaaagtgat tacatgtcat tcataaacaa ccccagtctt 3300 actgtgactg taccaattgc tgtaggagaa tctgactttg aaaatttaaa cacggaagac 3360 tttagtagtg aatcggatct ggaagaaagc aaagagaaac tgaatgaaag cagtagctca 3420 tcagaaggta gcactgtgga catcggcgca cctgtagaag aacagcccgt agtggaacct 3480 gaagaaactc ttgaaccaga agcttgtttc actgaaggct gtgtacaaag attcaagtgt 3540 tgtcaaatca atgtggaaga aggcagagga aaacaatggt ggaacctgag aaggacgtgt 3600 ttccgaatag ttgaacataa ctggtttgag accttcattg ttttcatgat tctccttagt 3660 agtggtgctc tggcatttga agatatatat attgatcagc gaaagacgat taagacgatg 3720 ttggaatatg ctgacaaggt tttcacttac attttcattc tggaaatgct tctaaaatgg 3780 gtggcatatg gctatcaaac atatttcacc aatgcctggt gttggctgga cttcttaatt 3840 gttgatgttt cattggtcag tttaacagca aatgccttgg gttactcaga acttggagcc 3900 atcaaatctc tcaggacact aagagctctg agacctctaa gagccttatc tcgatttgaa 3960 gggatgaggg tggttgtgaa tgccctttta ggagcaattc catccatcat gaatgtgctt 4020 ctggtttgtc ttatattctg gctaattttc agcatcatgg gcgtaaattt gtttgctggc 4080 aaattctacc actgtattaa caccacaact ggtgacaggt ttgacatcga agacgtgaat 4140 aatcatactg attgcctaaa actaatagaa agaaatgaga ctgctcgatg gaaaaatgtg 4200 aaagtaaact ttgataatgt aggatttggg tatctctctt tgcttcaagt tgccacattc 4260 aaaggatgga tggatataat gtatgcagca gttgattcca gaaatcctct ttcaggctcc 4320 aagacctaa 4329 6 1442 PRT homo sapiens VARIANT (1)...(1442) Xaa = Any Amino Acid 6 Met Glu Gln Thr Val Leu Val Pro Pro Gly Pro Asp Ser Phe Asn Phe 1 5 10 15 Phe Thr Arg Glu Ser Leu Ala Ala Ile Glu Arg Arg Ile Ala Glu Glu 20 25 30 Lys Ala Lys Asn Pro Lys Pro Asp Lys Lys Asp Asp Asp Glu Asn Gly 35 40 45 Pro Lys Pro Asn Ser Asp Leu Glu Ala Gly Lys Asn Leu Pro Phe Ile 50 55 60 Tyr Gly Asp Ile Pro Pro Glu Met Val Ser Glu Pro Leu Glu Asp Leu 65 70 75 80 Asp Pro Tyr Tyr Ile Asn Lys Lys Thr Phe Ile Val Leu Asn Lys Gly 85 90 95 Lys Ala Ile Phe Arg Phe Ser Ala Thr Ser Ala Leu Tyr Ile Leu Thr 100 105 110 Pro Phe Asn Pro Leu Arg Lys Ile Ala Ile Lys Ile Leu Val His Ser 115 120 125 Leu Phe Ser Met Leu Ile Met Cys Thr Ile Leu Thr Asn Cys Val Phe 130 135 140 Met Thr Met Ser Asn Pro Pro Asp Trp Thr Lys Asn Val Glu Tyr Thr 145 150 155 160 Phe Thr Gly Ile Tyr Thr Phe Glu Ser Leu Ile Lys Ile Ile Ala Arg 165 170 175 Gly Phe Cys Leu Glu Asp Phe Thr Phe Leu Arg Asp Pro Trp Asn Trp 180 185 190 Leu Asp Phe Thr Val Ile Thr Phe Ala Tyr Val Thr Glu Phe Val Asp 195 200 205 Leu Gly Asn Val Ser Ala Leu Arg Thr Phe Arg Val Leu Arg Ala Leu 210 215 220 Lys Thr Ile Ser Val Ile Pro Gly Leu Lys Thr Ile Val Gly Ala Leu 225 230 235 240 Ile Gln Ser Val Lys Lys Leu Ser Asp Val Met Ile Leu Thr Val Phe 245 250 255 Cys Leu Ser Val Phe Ala Leu Ile Gly Leu Gln Leu Phe Met Gly Asn 260 265 270 Leu Arg Asn Lys Cys Ile Gln Trp Pro Pro Thr Asn Ala Ser Leu Glu 275 280 285 Glu His Ser Ile Glu Lys Asn Ile Thr Val Asn Tyr Asn Gly Thr Leu 290 295 300 Ile Asn Glu Thr Val Phe Glu Phe Asp Trp Lys Ser Tyr Ile Gln Asp 305 310 315 320 Ser Arg Tyr His Tyr Phe Leu Glu Gly Phe Leu Asp Ala Leu Leu Cys 325 330 335 Gly Asn Ser Ser Asp Ala Gly Gln Cys Pro Glu Gly Tyr Met Cys Val 340 345 350 Lys Ala Gly Arg Asn Pro Asn Tyr Gly Tyr Thr Ser Phe Asp Thr Phe 355 360 365 Ser Trp Ala Phe Leu Ser Leu Phe Arg Leu Met Thr Gln Asp Phe Trp 370 375 380 Glu Asn Leu Tyr Gln Leu Thr Leu Arg Ala Ala Gly Lys Thr Tyr Met 385 390 395 400 Ile Phe Phe Val Leu Val Ile Phe Leu Gly Ser Phe Tyr Leu Ile Asn 405 410 415 Leu Ile Leu Ala Val Val Ala Met Ala Tyr Glu Glu Gln Asn Gln Ala 420 425 430 Thr Leu Glu Glu Ala Glu Gln Lys Glu Ala Glu Phe Gln Gln Met Ile 435 440 445 Glu Gln Leu Lys Lys Gln Gln Glu Ala Ala Gln Gln Ala Ala Thr Ala 450 455 460 Thr Ala Ser Glu His Ser Arg Glu Pro Ser Ala Ala Gly Arg Leu Ser 465 470 475 480 Asp Ser Ser Ser Glu Ala Ser Lys Leu Ser Ser Lys Ser Ala Lys Glu 485 490 495 Arg Arg Asn Arg Arg Lys Lys Arg Lys Gln Lys Glu Gln Ser Gly Gly 500 505 510 Glu Glu Lys Asp Glu Asp Glu Phe Gln Lys Ser Glu Ser Glu Asp Ser 515 520 525 Ile Arg Arg Lys Gly Phe Arg Phe Ser Ile Glu Gly Asn Arg Leu Thr 530 535 540 Tyr Glu Lys Arg Tyr Ser Ser Pro His Gln Ser Leu Leu Ser Ile Arg 545 550 555 560 Gly Ser Leu Phe Ser Pro Arg Arg Asn Ser Arg Thr Ser Leu Phe Ser 565 570 575 Phe Arg Gly Arg Ala Lys Asp Val Gly Ser Glu Asn Asp Phe Ala Asp 580 585 590 Asp Glu His Ser Thr Phe Glu Asp Asn Glu Ser Arg Arg Asp Ser Leu 595 600 605 Phe Val Pro Arg Arg His Gly Glu Arg Arg Asn Ser Asn Leu Ser Gln 610 615 620 Thr Ser Arg Ser Ser Arg Met Leu Ala Val Phe Pro Ala Asn Gly Lys 625 630 635 640 Met His Ser Thr Val Asp Cys Asn Gly Val Val Ser Leu Val Gly Gly 645 650 655 Pro Ser Val Pro Thr Ser Pro Val Gly Gln Leu Leu Pro Glu Gly Thr 660 665 670 Thr Thr Glu Thr Glu Met Arg Lys Arg Arg Ser Ser Ser Phe His Val 675 680 685 Ser Met Asp Phe Leu Glu Asp Pro Ser Gln Arg Gln Arg Ala Met Ser 690 695 700 Ile Ala Ser Ile Leu Thr Asn Thr Val Glu Glu Leu Glu Glu Ser Arg 705 710 715 720 Gln Lys Cys Pro Pro Cys Trp Tyr Lys Phe Ser Asn Ile Phe Leu Ile 725 730 735 Trp Asp Cys Ser Pro Tyr Trp Leu Lys Val Lys His Val Val Asn Leu 740 745 750 Val Val Met Asp Pro Phe Val Asp Leu Ala Ile Thr Ile Cys Ile Val 755 760 765 Leu Asn Thr Leu Phe Met Ala Met Glu His Tyr Pro Met Thr Asp His 770 775 780 Phe Asn Asn Val Leu Thr Val Gly Asn Leu Val Phe Thr Gly Ile Phe 785 790 795 800 Thr Ala Glu Met Phe Leu Lys Ile Ile Ala Met Asp Pro Tyr Tyr Tyr 805 810 815 Phe Gln Glu Gly Trp Asn Ile Phe Asp Gly Phe Ile Val Thr Leu Ser 820 825 830 Leu Val Glu Leu Gly Leu Ala Asn Val Glu Gly Leu Ser Val Leu Arg 835 840 845 Ser Phe Arg Leu Leu Arg Val Phe Lys Leu Ala Lys Ser Trp Pro Thr 850 855 860 Leu Asn Met Leu Ile Lys Ile Ile Gly Asn Ser Val Gly Ala Leu Gly 865 870 875 880 Asn Leu Thr Leu Val Leu Ala Ile Ile Val Phe Ile Phe Ala Val Val 885 890 895 Gly Met Gln Leu Phe Gly Lys Ser Tyr Lys Asp Cys Val Cys Lys Ile 900 905 910 Ala Ser Asp Cys Gln Leu Pro Arg Trp His Met Asn Asp Phe Phe His 915 920 925 Ser Phe Leu Ile Val Phe Arg Val Leu Cys Gly Glu Trp Ile Glu Thr 930 935 940 Met Trp Asp Cys Met Glu Val Ala Gly Gln Ala Met Cys Leu Thr Val 945 950 955 960 Phe Met Met Val Met Val Ile Gly Asn Leu Val Val Leu Asn Leu Phe 965 970 975 Leu Ala Leu Leu Xaa Ser Ser Phe Ser Ala Asp Asn Leu Ala Ala Thr 980 985 990 Asp Asp Asp Asn Glu Met Asn Asn Leu Gln Ile Ala Val Asp Arg Met 995 1000 1005 His Lys Gly Val Ala Tyr Val Lys Arg Lys Ile Tyr Glu Phe Ile Gln 1010 1015 1020 Gln Ser Phe Ile Arg Lys Gln Lys Ile Leu Asp Glu Ile Lys Pro Leu 1025 1030 1035 1040 Asp Asp Leu Asn Asn Lys Lys Asp Ser Cys Met Ser Asn His Thr Xaa 1045 1050 1055 Glu Ile Gly Lys Asp Leu Asp Tyr Leu Lys Asp Val Asn Gly Thr Thr 1060 1065 1070 Ser Gly Ile Gly Thr Gly Ser Ser Val Glu Lys Tyr Ile Ile Asp Glu 1075 1080 1085 Ser Asp Tyr Met Ser Phe Ile Asn Asn Pro Ser Leu Thr Val Thr Val 1090 1095 1100 Pro Ile Ala Val Gly Glu Ser Asp Phe Glu Asn Leu Asn Thr Glu Asp 1105 1110 1115 1120 Phe Ser Ser Glu Ser Asp Leu Glu Glu Ser Lys Glu Lys Leu Asn Glu 1125 1130 1135 Ser Ser Ser Ser Ser Glu Gly Ser Thr Val Asp Ile Gly Ala Pro Val 1140 1145 1150 Glu Glu Gln Pro Val Val Glu Pro Glu Glu Thr Leu Glu Pro Glu Ala 1155 1160 1165 Cys Phe Thr Glu Gly Cys Val Gln Arg Phe Lys Cys Cys Gln Ile Asn 1170 1175 1180 Val Glu Glu Gly Arg Gly Lys Gln Trp Trp Asn Leu Arg Arg Thr Cys 1185 1190 1195 1200 Phe Arg Ile Val Glu His Asn Trp Phe Glu Thr Phe Ile Val Phe Met 1205 1210 1215 Ile Leu Leu Ser Ser Gly Ala Leu Ala Phe Glu Asp Ile Tyr Ile Asp 1220 1225 1230 Gln Arg Lys Thr Ile Lys Thr Met Leu Glu Tyr Ala Asp Lys Val Phe 1235 1240 1245 Thr Tyr Ile Phe Ile Leu Glu Met Leu Leu Lys Trp Val Ala Tyr Gly 1250 1255 1260 Tyr Gln Thr Tyr Phe Thr Asn Ala Trp Cys Trp Leu Asp Phe Leu Ile 1265 1270 1275 1280 Val Asp Val Ser Leu Val Ser Leu Thr Ala Asn Ala Leu Gly Tyr Ser 1285 1290 1295 Glu Leu Gly Ala Ile Lys Ser Leu Arg Thr Leu Arg Ala Leu Arg Pro 1300 1305 1310 Leu Arg Ala Leu Ser Arg Phe Glu Gly Met Arg Val Val Val Asn Ala 1315 1320 1325 Leu Leu Gly Ala Ile Pro Ser Ile Met Asn Val Leu Leu Val Cys Leu 1330 1335 1340 Ile Phe Trp Leu Ile Phe Ser Ile Met Gly Val Asn Leu Phe Ala Gly 1345 1350 1355 1360 Lys Phe Tyr His Cys Ile Asn Thr Thr Thr Gly Asp Arg Phe Asp Ile 1365 1370 1375 Glu Asp Val Asn Asn His Thr Asp Cys Leu Lys Leu Ile Glu Arg Asn 1380 1385 1390 Glu Thr Ala Arg Trp Lys Asn Val Lys Val Asn Phe Asp Asn Val Gly 1395 1400 1405 Phe Gly Tyr Leu Ser Leu Leu Gln Val Ala Thr Phe Lys Gly Trp Met 1410 1415 1420 Asp Ile Met Tyr Ala Ala Val Asp Ser Arg Asn Pro Leu Ser Gly Ser 1425 1430 1435 1440 Lys Thr 7 4146 DNA homo sapiens 7 atggagcaaa cagtgcttgt accaccagga cctgacagct tcaacttctt caccagagaa 60 tctcttgcgg ctattgaaag acgcattgca gaagaaaagg caaagaatcc caaaccagac 120 aaaaaagatg acgacgaaaa tggcccaaag ccaaatagtg acttggaagc tggaaagaac 180 cttccattta tttatggaga cattcctcca gagatggtgt cagagcccct ggaggacctg 240 gacccctact atatcaataa gaaaactttt atagtattga ataaagggaa ggccatcttc 300 cggttcagtg ccacctctgc cctgtacatt ttaactccct tcaatcctct taggaaaata 360 gctattaaga ttttggtaca ttcattattc agcatgctaa ttatgtgcac tattttgaca 420 aactgtgtgt ttatgacaat gagtaaccct cctgattgga caaagaatgt agaatacacc 480 ttcacaggaa tatatacttt tgaatcactt ataaaaatta ttgcaagggg attctgttta 540 gaagatttta ctttccttcg ggatccatgg aactggctcg atttcactgt cattacattt 600 gcgtacgtca cagagtttgt ggacctgggc aatgtctcgg cattgagaac attcagagtt 660 ctccgagcat tgaagacgat ttcagtcatt ccaggcctga aaaccattgt gggagccctg 720 atccagtctg tgaagaagct ctcagatgta atgatcctga ctgtgttctg tctgagcgta 780 tttgctctaa ttgggctgca gctgttcatg ggcaacctga ggaataaatg tatacaatgg 840 cctcccacca atgcttcctt ggaggaacat agtatagaaa agaatataac tgtgaattat 900 aatggtacac ttataaatga aactgtcttt gagtttgact ggaagtcata tattcaagat 960 tcaagatatc attatttcct ggagggtttt ttagatgcac tactatgtgg aaatagctct 1020 gatgcaggcc aatgtccaga gggatatatg tgtgtgaaag ctggtagaaa tcccaattat 1080 ggctacacaa gctttgatac cttcagttgg gcttttttgt ccttgtttcg actaatgact 1140 caggacttct gggaaaatct ttatcaactg acattacgtg ctgctgggaa aacgtacatg 1200 atattttttg tgttggtcat tttcttgggc tcattctacc taataaattt gatcctggct 1260 gtggtggcca tggcctacga ggaacagaat caggccacct tggaagaagc agaacagaaa 1320 gaggccgaat ttcagcagat gattgaacag cttaaaaagc aacaggaggc agctcagcag 1380 gcagcaacgg caactgcctc agaacattcc agagagccca gtgcagcagg caggctctca 1440 gacagctcat ctgaagcctc taagttgagt tccaagagtg ctaaggaaag aagaaatcgg 1500 aggaagaaaa gaaaacagaa agagcagtct ggtggggaag agaaagatga ggatgaattc 1560 caaaaatctg aatctgagga cagcatcagg aggaaaggtt ttcgcttctc cattgaaggg 1620 aaccgattga catatgaaaa gaggtactcc tccccacacc agtctttgtt gagcatccgt 1680 ggctccctat tttcaccaag gcgaaatagc agaacaagcc ttttcagctt tagagggcga 1740 gcaaaggatg tgggatctga gaacgacttc gcagatgatg agcacagcac ctttgaggat 1800 aacgagagcc gtagagattc cttgtttgtg ccccgacgac acggagagag acgcaacagc 1860 aacctgagtc agaccagtag gtcatcccgg atgctggcag tgtttccagc gaatgggaag 1920 atgcacagca ctgtggattg caatggtgtg gtttccttgg ttggtggacc ttcagttcct 1980 acatcgcctg ttggacagct tctgccagag ggaacaacca ctgaaactga aatgagaaag 2040 agaaggtcaa gttctttcca cgtttccatg gactttctag aagatccttc ccaaaggcaa 2100 cgagcaatga gtatagccag cattctaaca aatacagtag aagaacttga agaatccagg 2160 cagaaatgcc caccctgttg gtataaattt tccaacatat tcttaatctg ggactgttct 2220 ccatattggt taaaagtgaa acatgttgtc aacctggtyg tgatggaccc atttgttgac 2280 ctggccatca ccatctgtat tgtcttaaat actcttttca tggccatgga gcactatcca 2340 atgacggacc atttcaataa tgtgcttaca gtaggaaact tggttttcac tgggatcttt 2400 acagcagaaa tgtttctgaa aattattgcc atggatcctt actattattt ccaagaaggc 2460 tggaatatct ttgacggttt tattgtgacg cttagcctgg tagaacttgg actcgccaat 2520 gtggaaggat tatctgttct ccgttcattt cgattgctgc gagttttcaa gttggcaaaa 2580 tcttggccaa cgttaaatat gctaataaag atcatcggca attccgtggg ggctctggga 2640 aatttaaccc tcgtcttggc catcatcgtc ttcatttttg ccgtggtcgg catgcagctc 2700 tttggtaaaa gctacaaaga ttgtgtctgc aagatcgcca gtgattgtca actcccacgc 2760 tggcacatga atgacttctt ccactccttc ctgattgtgt tccgcgtgct gtgtggggag 2820 tggatagaga ccatgtggga ctgtatggag gttgctggtc aagccatgtg ccttactgtc 2880 ttcatgatgg tcatggtgat tggaaaccta gtggtcctga atctctttct ggccttgctt 2940 mtgagctcat ttagtgcaga caaccttgca gccactgatg atgataatga aatgaataat 3000 ctccaaattg ctgtggatag gatgcacaaa ggagtagctt atgtgaaaag aaaaatatat 3060 gaatttattc aacagtcctt cattaggaaa caaaagattt tagatgaaat taaaccactt 3120 gatgatctaa acaacaagaa agacagttgt atgtccaatc atacarcaga aattgggaaa 3180 gatcttgact atcttaaaga tgtaaatgga actacaagtg gtataggaac tggcagcagt 3240 gttgaaaaat acattattga tgaaagtgat tacatgtcat tcataaacaa ccccagtctt 3300 actgtgactg taccaattgc tgtaggagaa tctgactttg aaaatttaaa cacggaagac 3360 tttagtagtg aatcggatct ggaagaaagc aaagagaaac tgaatgaaag cagtagctca 3420 tcagaaggta gcactgtgga catcggcgca cctgtagaag aacagcccgt agtggaacct 3480 gaagaaactc ttgaaccaga agcttgtttc actgaaggct gtgtacaaag attcaagtgt 3540 tgtcaaatca atgtggaaga aggcagagga aaacaatggt ggaacctgag aaggacgtgt 3600 ttccgaatag ttgaacataa ctggtttgag accttcattg ttttcatgat tctccttagt 3660 agtggtgctc tggcatttga agatatatat attgatcagc gaaagacgat taagacgatg 3720 ttggaatatg ctgacaaggt tttcacttac attttcattc tggaaatgct tctaaaatgg 3780 gtggcatatg gctatcaaac atatttcacc aatgcctggt gttggctgga cttcttaatt 3840 gttgatgttt cattggtcag tttaacagca aatgccttgg gttactcaga acttggagcc 3900 atcaaatctc tcaggacact aagagctctg agacctctaa gagccttatc tcgatttgaa 3960 gggatgaggg tggttgtgaa tgccctttta ggagcaattc catccatcat gaatgtgctt 4020 ctggtttgtc ttatattctg gctaattttc agcatcatgg gcgtaaattt gtttgctggc 4080 aaattctacc actgtattaa caccacaact ggtgacaggc cacattcaaa ggatggatgg 4140 atataa 4146 8 1381 PRT homo sapiens VARIANT (1)...(1381) Xaa = Any Amino Acid 8 Met Glu Gln Thr Val Leu Val Pro Pro Gly Pro Asp Ser Phe Asn Phe 1 5 10 15 Phe Thr Arg Glu Ser Leu Ala Ala Ile Glu Arg Arg Ile Ala Glu Glu 20 25 30 Lys Ala Lys Asn Pro Lys Pro Asp Lys Lys Asp Asp Asp Glu Asn Gly 35 40 45 Pro Lys Pro Asn Ser Asp Leu Glu Ala Gly Lys Asn Leu Pro Phe Ile 50 55 60 Tyr Gly Asp Ile Pro Pro Glu Met Val Ser Glu Pro Leu Glu Asp Leu 65 70 75 80 Asp Pro Tyr Tyr Ile Asn Lys Lys Thr Phe Ile Val Leu Asn Lys Gly 85 90 95 Lys Ala Ile Phe Arg Phe Ser Ala Thr Ser Ala Leu Tyr Ile Leu Thr 100 105 110 Pro Phe Asn Pro Leu Arg Lys Ile Ala Ile Lys Ile Leu Val His Ser 115 120 125 Leu Phe Ser Met Leu Ile Met Cys Thr Ile Leu Thr Asn Cys Val Phe 130 135 140 Met Thr Met Ser Asn Pro Pro Asp Trp Thr Lys Asn Val Glu Tyr Thr 145 150 155 160 Phe Thr Gly Ile Tyr Thr Phe Glu Ser Leu Ile Lys Ile Ile Ala Arg 165 170 175 Gly Phe Cys Leu Glu Asp Phe Thr Phe Leu Arg Asp Pro Trp Asn Trp 180 185 190 Leu Asp Phe Thr Val Ile Thr Phe Ala Tyr Val Thr Glu Phe Val Asp 195 200 205 Leu Gly Asn Val Ser Ala Leu Arg Thr Phe Arg Val Leu Arg Ala Leu 210 215 220 Lys Thr Ile Ser Val Ile Pro Gly Leu Lys Thr Ile Val Gly Ala Leu 225 230 235 240 Ile Gln Ser Val Lys Lys Leu Ser Asp Val Met Ile Leu Thr Val Phe 245 250 255 Cys Leu Ser Val Phe Ala Leu Ile Gly Leu Gln Leu Phe Met Gly Asn 260 265 270 Leu Arg Asn Lys Cys Ile Gln Trp Pro Pro Thr Asn Ala Ser Leu Glu 275 280 285 Glu His Ser Ile Glu Lys Asn Ile Thr Val Asn Tyr Asn Gly Thr Leu 290 295 300 Ile Asn Glu Thr Val Phe Glu Phe Asp Trp Lys Ser Tyr Ile Gln Asp 305 310 315 320 Ser Arg Tyr His Tyr Phe Leu Glu Gly Phe Leu Asp Ala Leu Leu Cys 325 330 335 Gly Asn Ser Ser Asp Ala Gly Gln Cys Pro Glu Gly Tyr Met Cys Val 340 345 350 Lys Ala Gly Arg Asn Pro Asn Tyr Gly Tyr Thr Ser Phe Asp Thr Phe 355 360 365 Ser Trp Ala Phe Leu Ser Leu Phe Arg Leu Met Thr Gln Asp Phe Trp 370 375 380 Glu Asn Leu Tyr Gln Leu Thr Leu Arg Ala Ala Gly Lys Thr Tyr Met 385 390 395 400 Ile Phe Phe Val Leu Val Ile Phe Leu Gly Ser Phe Tyr Leu Ile Asn 405 410 415 Leu Ile Leu Ala Val Val Ala Met Ala Tyr Glu Glu Gln Asn Gln Ala 420 425 430 Thr Leu Glu Glu Ala Glu Gln Lys Glu Ala Glu Phe Gln Gln Met Ile 435 440 445 Glu Gln Leu Lys Lys Gln Gln Glu Ala Ala Gln Gln Ala Ala Thr Ala 450 455 460 Thr Ala Ser Glu His Ser Arg Glu Pro Ser Ala Ala Gly Arg Leu Ser 465 470 475 480 Asp Ser Ser Ser Glu Ala Ser Lys Leu Ser Ser Lys Ser Ala Lys Glu 485 490 495 Arg Arg Asn Arg Arg Lys Lys Arg Lys Gln Lys Glu Gln Ser Gly Gly 500 505 510 Glu Glu Lys Asp Glu Asp Glu Phe Gln Lys Ser Glu Ser Glu Asp Ser 515 520 525 Ile Arg Arg Lys Gly Phe Arg Phe Ser Ile Glu Gly Asn Arg Leu Thr 530 535 540 Tyr Glu Lys Arg Tyr Ser Ser Pro His Gln Ser Leu Leu Ser Ile Arg 545 550 555 560 Gly Ser Leu Phe Ser Pro Arg Arg Asn Ser Arg Thr Ser Leu Phe Ser 565 570 575 Phe Arg Gly Arg Ala Lys Asp Val Gly Ser Glu Asn Asp Phe Ala Asp 580 585 590 Asp Glu His Ser Thr Phe Glu Asp Asn Glu Ser Arg Arg Asp Ser Leu 595 600 605 Phe Val Pro Arg Arg His Gly Glu Arg Arg Asn Ser Asn Leu Ser Gln 610 615 620 Thr Ser Arg Ser Ser Arg Met Leu Ala Val Phe Pro Ala Asn Gly Lys 625 630 635 640 Met His Ser Thr Val Asp Cys Asn Gly Val Val Ser Leu Val Gly Gly 645 650 655 Pro Ser Val Pro Thr Ser Pro Val Gly Gln Leu Leu Pro Glu Gly Thr 660 665 670 Thr Thr Glu Thr Glu Met Arg Lys Arg Arg Ser Ser Ser Phe His Val 675 680 685 Ser Met Asp Phe Leu Glu Asp Pro Ser Gln Arg Gln Arg Ala Met Ser 690 695 700 Ile Ala Ser Ile Leu Thr Asn Thr Val Glu Glu Leu Glu Glu Ser Arg 705 710 715 720 Gln Lys Cys Pro Pro Cys Trp Tyr Lys Phe Ser Asn Ile Phe Leu Ile 725 730 735 Trp Asp Cys Ser Pro Tyr Trp Leu Lys Val Lys His Val Val Asn Leu 740 745 750 Val Val Met Asp Pro Phe Val Asp Leu Ala Ile Thr Ile Cys Ile Val 755 760 765 Leu Asn Thr Leu Phe Met Ala Met Glu His Tyr Pro Met Thr Asp His 770 775 780 Phe Asn Asn Val Leu Thr Val Gly Asn Leu Val Phe Thr Gly Ile Phe 785 790 795 800 Thr Ala Glu Met Phe Leu Lys Ile Ile Ala Met Asp Pro Tyr Tyr Tyr 805 810 815 Phe Gln Glu Gly Trp Asn Ile Phe Asp Gly Phe Ile Val Thr Leu Ser 820 825 830 Leu Val Glu Leu Gly Leu Ala Asn Val Glu Gly Leu Ser Val Leu Arg 835 840 845 Ser Phe Arg Leu Leu Arg Val Phe Lys Leu Ala Lys Ser Trp Pro Thr 850 855 860 Leu Asn Met Leu Ile Lys Ile Ile Gly Asn Ser Val Gly Ala Leu Gly 865 870 875 880 Asn Leu Thr Leu Val Leu Ala Ile Ile Val Phe Ile Phe Ala Val Val 885 890 895 Gly Met Gln Leu Phe Gly Lys Ser Tyr Lys Asp Cys Val Cys Lys Ile 900 905 910 Ala Ser Asp Cys Gln Leu Pro Arg Trp His Met Asn Asp Phe Phe His 915 920 925 Ser Phe Leu Ile Val Phe Arg Val Leu Cys Gly Glu Trp Ile Glu Thr 930 935 940 Met Trp Asp Cys Met Glu Val Ala Gly Gln Ala Met Cys Leu Thr Val 945 950 955 960 Phe Met Met Val Met Val Ile Gly Asn Leu Val Val Leu Asn Leu Phe 965 970 975 Leu Ala Leu Leu Xaa Ser Ser Phe Ser Ala Asp Asn Leu Ala Ala Thr 980 985 990 Asp Asp Asp Asn Glu Met Asn Asn Leu Gln Ile Ala Val Asp Arg Met 995 1000 1005 His Lys Gly Val Ala Tyr Val Lys Arg Lys Ile Tyr Glu Phe Ile Gln 1010 1015 1020 Gln Ser Phe Ile Arg Lys Gln Lys Ile Leu Asp Glu Ile Lys Pro Leu 1025 1030 1035 1040 Asp Asp Leu Asn Asn Lys Lys Asp Ser Cys Met Ser Asn His Thr Xaa 1045 1050 1055 Glu Ile Gly Lys Asp Leu Asp Tyr Leu Lys Asp Val Asn Gly Thr Thr 1060 1065 1070 Ser Gly Ile Gly Thr Gly Ser Ser Val Glu Lys Tyr Ile Ile Asp Glu 1075 1080 1085 Ser Asp Tyr Met Ser Phe Ile Asn Asn Pro Ser Leu Thr Val Thr Val 1090 1095 1100 Pro Ile Ala Val Gly Glu Ser Asp Phe Glu Asn Leu Asn Thr Glu Asp 1105 1110 1115 1120 Phe Ser Ser Glu Ser Asp Leu Glu Glu Ser Lys Glu Lys Leu Asn Glu 1125 1130 1135 Ser Ser Ser Ser Ser Glu Gly Ser Thr Val Asp Ile Gly Ala Pro Val 1140 1145 1150 Glu Glu Gln Pro Val Val Glu Pro Glu Glu Thr Leu Glu Pro Glu Ala 1155 1160 1165 Cys Phe Thr Glu Gly Cys Val Gln Arg Phe Lys Cys Cys Gln Ile Asn 1170 1175 1180 Val Glu Glu Gly Arg Gly Lys Gln Trp Trp Asn Leu Arg Arg Thr Cys 1185 1190 1195 1200 Phe Arg Ile Val Glu His Asn Trp Phe Glu Thr Phe Ile Val Phe Met 1205 1210 1215 Ile Leu Leu Ser Ser Gly Ala Leu Ala Phe Glu Asp Ile Tyr Ile Asp 1220 1225 1230 Gln Arg Lys Thr Ile Lys Thr Met Leu Glu Tyr Ala Asp Lys Val Phe 1235 1240 1245 Thr Tyr Ile Phe Ile Leu Glu Met Leu Leu Lys Trp Val Ala Tyr Gly 1250 1255 1260 Tyr Gln Thr Tyr Phe Thr Asn Ala Trp Cys Trp Leu Asp Phe Leu Ile 1265 1270 1275 1280 Val Asp Val Ser Leu Val Ser Leu Thr Ala Asn Ala Leu Gly Tyr Ser 1285 1290 1295 Glu Leu Gly Ala Ile Lys Ser Leu Arg Thr Leu Arg Ala Leu Arg Pro 1300 1305 1310 Leu Arg Ala Leu Ser Arg Phe Glu Gly Met Arg Val Val Val Asn Ala 1315 1320 1325 Leu Leu Gly Ala Ile Pro Ser Ile Met Asn Val Leu Leu Val Cys Leu 1330 1335 1340 Ile Phe Trp Leu Ile Phe Ser Ile Met Gly Val Asn Leu Phe Ala Gly 1345 1350 1355 1360 Lys Phe Tyr His Cys Ile Asn Thr Thr Thr Gly Asp Arg Pro His Ser 1365 1370 1375 Lys Asp Gly Trp Ile 1380 9 4164 DNA homo sapiens 9 atggagcaaa cagtgcttgt accaccagga cctgacagct tcaacttctt caccagagaa 60 tctcttgcgg ctattgaaag acgcattgca gaagaaaagg caaagaatcc caaaccagac 120 aaaaaagatg acgacgaaaa tggcccaaag ccaaatagtg acttggaagc tggaaagaac 180 cttccattta tttatggaga cattcctcca gagatggtgt cagagcccct ggaggacctg 240 gacccctact atatcaataa gaaaactttt atagtattga ataaagggaa ggccatcttc 300 cggttcagtg ccacctctgc cctgtacatt ttaactccct tcaatcctct taggaaaata 360 gctattaaga ttttggtaca ttcattattc agcatgctaa ttatgtgcac tattttgaca 420 aactgtgtgt ttatgacaat gagtaaccct cctgattgga caaagaatgt agaatacacc 480 ttcacaggaa tatatacttt tgaatcactt ataaaaatta ttgcaagggg attctgttta 540 gaagatttta ctttccttcg ggatccatgg aactggctcg atttcactgt cattacattt 600 gcgtacgtca cagagtttgt ggacctgggc aatgtctcgg cattgagaac attcagagtt 660 ctccgagcat tgaagacgat ttcagtcatt ccaggcctga aaaccattgt gggagccctg 720 atccagtctg tgaagaagct ctcagatgta atgatcctga ctgtgttctg tctgagcgta 780 tttgctctaa ttgggctgca gctgttcatg ggcaacctga ggaataaatg tatacaatgg 840 cctcccacca atgcttcctt ggaggaacat agtatagaaa agaatataac tgtgaattat 900 aatggtacac ttataaatga aactgtcttt gagtttgact ggaagtcata tattcaagat 960 tcaagatatc attatttcct ggagggtttt ttagatgcac tactatgtgg aaatagctct 1020 gatgcaggcc aatgtccaga gggatatatg tgtgtgaaag ctggtagaaa tcccaattat 1080 ggctacacaa gctttgatac cttcagttgg gcttttttgt ccttgtttcg actaatgact 1140 caggacttct gggaaaatct ttatcaactg acattacgtg ctgctgggaa aacgtacatg 1200 atattttttg tgttggtcat tttcttgggc tcattctacc taataaattt gatcctggct 1260 gtggtggcca tggcctacga ggaacagaat caggccacct tggaagaagc agaacagaaa 1320 gaggccgaat ttcagcagat gattgaacag cttaaaaagc aacaggaggc agctcagcag 1380 gcagcaacgg caactgcctc agaacattcc agagagccca gtgcagcagg caggctctca 1440 gacagctcat ctgaagcctc taagttgagt tccaagagtg ctaaggaaag aagaaatcgg 1500 aggaagaaaa gaaaacagaa agagcagtct ggtggggaag agaaagatga ggatgaattc 1560 caaaaatctg aatctgagga cagcatcagg aggaaaggtt ttcgcttctc cattgaaggg 1620 aaccgattga catatgaaaa gaggtactcc tccccacacc agtctttgtt gagcatccgt 1680 ggctccctat tttcaccaag gcgaaatagc agaacaagcc ttttcagctt tagagggcga 1740 gcaaaggatg tgggatctga gaacgacttc gcagatgatg agcacagcac ctttgaggat 1800 aacgagagcc gtagagattc cttgtttgtg ccccgacgac acggagagag acgcaacagc 1860 aacctgagtc agaccagtag gtcatcccgg atgctggcag tgtttccagc gaatgggaag 1920 atgcacagca ctgtggattg caatggtgtg gtttccttgg ttggtggacc ttcagttcct 1980 acatcgcctg ttggacagct tctgccagag ggaacaacca ctgaaactga aatgagaaag 2040 agaaggtcaa gttctttcca cgtttccatg gactttctag aagatccttc ccaaaggcaa 2100 cgagcaatga gtatagccag cattctaaca aatacagtag aagaacttga agaatccagg 2160 cagaaatgcc caccctgttg gtataaattt tccaacatat tcttaatctg ggactgttct 2220 ccatattggt taaaagtgaa acatgttgtc aacctggtyg tgatggaccc atttgttgac 2280 ctggccatca ccatctgtat tgtcttaaat actcttttca tggccatgga gcactatcca 2340 atgacggacc atttcaataa tgtgcttaca gtaggaaact tggttttcac tgggatcttt 2400 acagcagaaa tgtttctgaa aattattgcc atggatcctt actattattt ccaagaaggc 2460 tggaatatct ttgacggttt tattgtgacg cttagcctgg tagaacttgg actcgccaat 2520 gtggaaggat tatctgttct ccgttcattt cgattgctgc gagttttcaa gttggcaaaa 2580 tcttggccaa cgttaaatat gctaataaag atcatcggca attccgtggg ggctctggga 2640 aatttaaccc tcgtcttggc catcatcgtc ttcatttttg ccgtggtcgg catgcagctc 2700 tttggtaaaa gctacaaaga ttgtgtctgc aagatcgcca gtgattgtca actcccacgc 2760 tggcacatga atgacttctt ccactccttc ctgattgtgt tccgcgtgct gtgtggggag 2820 tggatagaga ccatgtggga ctgtatggag gttgctggtc aagccatgtg ccttactgtc 2880 ttcatgatgg tcatggtgat tggaaaccta gtggtcctga atctctttct ggccttgctt 2940 mtgagctcat ttagtgcaga caaccttgca gccactgatg atgataatga aatgaataat 3000 ctccaaattg ctgtggatag gatgcacaaa ggagtagctt atgtgaaaag aaaaatatat 3060 gaatttattc aacagtcctt cattaggaaa caaaagattt tagatgaaat taaaccactt 3120 gatgatctaa acaacaagaa agacagttgt atgtccaatc atacarcaga aattgggaaa 3180 gatcttgact atcttaaaga tgtaaatgga actacaagtg gtataggaac tggcagcagt 3240 gttgaaaaat acattattga tgaaagtgat tacatgtcat tcataaacaa ccccagtctt 3300 actgtgactg taccaattgc tgtaggagaa tctgactttg aaaatttaaa cacggaagac 3360 tttagtagtg aatcggatct ggaagaaagc aaagagaaac tgaatgaaag cagtagctca 3420 tcagaaggta gcactgtgga catcggcgca cctgtagaag aacagcccgt agtggaacct 3480 gaagaaactc ttgaaccaga agcttgtttc actgaaggct gtgtacaaag attcaagtgt 3540 tgtcaaatca atgtggaaga aggcagagga aaacaatggt ggaacctgag aaggacgtgt 3600 ttccgaatag ttgaacataa ctggtttgag accttcattg ttttcatgat tctccttagt 3660 agtggtgctc tggcatttga agatatatat attgatcagc gaaagacgat taagacgatg 3720 ttggaatatg ctgacaaggt tttcacttac attttcattc tggaaatgct tctaaaatgg 3780 gtggcatatg gctatcaaac atatttcacc aatgcctggt gttggctgga cttcttaatt 3840 gttgatgttt cattggtcag tttaacagca aatgccttgg gttactcaga acttggagcc 3900 atcaaatctc tcaggacact aagagctctg agacctctaa gagccttatc tcgatttgaa 3960 gggatgaggg ataatcttgc tccaacttgg atggggtgga gcgctggttc ctcccctgag 4020 ccctttatta tgggtggttg tgaatgccct tttaggagca attccatcca tcatgaatgt 4080 gcttctggtt tgtcttatat tctggctaat tttcagcatc atgggcgtaa atttgtttgc 4140 tggcaaattc taccactgta ttaa 4164 10 1387 PRT homo sapiens VARIANT (1)...(1387) Xaa = Any Amino Acid 10 Met Glu Gln Thr Val Leu Val Pro Pro Gly Pro Asp Ser Phe Asn Phe 1 5 10 15 Phe Thr Arg Glu Ser Leu Ala Ala Ile Glu Arg Arg Ile Ala Glu Glu 20 25 30 Lys Ala Lys Asn Pro Lys Pro Asp Lys Lys Asp Asp Asp Glu Asn Gly 35 40 45 Pro Lys Pro Asn Ser Asp Leu Glu Ala Gly Lys Asn Leu Pro Phe Ile 50 55 60 Tyr Gly Asp Ile Pro Pro Glu Met Val Ser Glu Pro Leu Glu Asp Leu 65 70 75 80 Asp Pro Tyr Tyr Ile Asn Lys Lys Thr Phe Ile Val Leu Asn Lys Gly 85 90 95 Lys Ala Ile Phe Arg Phe Ser Ala Thr Ser Ala Leu Tyr Ile Leu Thr 100 105 110 Pro Phe Asn Pro Leu Arg Lys Ile Ala Ile Lys Ile Leu Val His Ser 115 120 125 Leu Phe Ser Met Leu Ile Met Cys Thr Ile Leu Thr Asn Cys Val Phe 130 135 140 Met Thr Met Ser Asn Pro Pro Asp Trp Thr Lys Asn Val Glu Tyr Thr 145 150 155 160 Phe Thr Gly Ile Tyr Thr Phe Glu Ser Leu Ile Lys Ile Ile Ala Arg 165 170 175 Gly Phe Cys Leu Glu Asp Phe Thr Phe Leu Arg Asp Pro Trp Asn Trp 180 185 190 Leu Asp Phe Thr Val Ile Thr Phe Ala Tyr Val Thr Glu Phe Val Asp 195 200 205 Leu Gly Asn Val Ser Ala Leu Arg Thr Phe Arg Val Leu Arg Ala Leu 210 215 220 Lys Thr Ile Ser Val Ile Pro Gly Leu Lys Thr Ile Val Gly Ala Leu 225 230 235 240 Ile Gln Ser Val Lys Lys Leu Ser Asp Val Met Ile Leu Thr Val Phe 245 250 255 Cys Leu Ser Val Phe Ala Leu Ile Gly Leu Gln Leu Phe Met Gly Asn 260 265 270 Leu Arg Asn Lys Cys Ile Gln Trp Pro Pro Thr Asn Ala Ser Leu Glu 275 280 285 Glu His Ser Ile Glu Lys Asn Ile Thr Val Asn Tyr Asn Gly Thr Leu 290 295 300 Ile Asn Glu Thr Val Phe Glu Phe Asp Trp Lys Ser Tyr Ile Gln Asp 305 310 315 320 Ser Arg Tyr His Tyr Phe Leu Glu Gly Phe Leu Asp Ala Leu Leu Cys 325 330 335 Gly Asn Ser Ser Asp Ala Gly Gln Cys Pro Glu Gly Tyr Met Cys Val 340 345 350 Lys Ala Gly Arg Asn Pro Asn Tyr Gly Tyr Thr Ser Phe Asp Thr Phe 355 360 365 Ser Trp Ala Phe Leu Ser Leu Phe Arg Leu Met Thr Gln Asp Phe Trp 370 375 380 Glu Asn Leu Tyr Gln Leu Thr Leu Arg Ala Ala Gly Lys Thr Tyr Met 385 390 395 400 Ile Phe Phe Val Leu Val Ile Phe Leu Gly Ser Phe Tyr Leu Ile Asn 405 410 415 Leu Ile Leu Ala Val Val Ala Met Ala Tyr Glu Glu Gln Asn Gln Ala 420 425 430 Thr Leu Glu Glu Ala Glu Gln Lys Glu Ala Glu Phe Gln Gln Met Ile 435 440 445 Glu Gln Leu Lys Lys Gln Gln Glu Ala Ala Gln Gln Ala Ala Thr Ala 450 455 460 Thr Ala Ser Glu His Ser Arg Glu Pro Ser Ala Ala Gly Arg Leu Ser 465 470 475 480 Asp Ser Ser Ser Glu Ala Ser Lys Leu Ser Ser Lys Ser Ala Lys Glu 485 490 495 Arg Arg Asn Arg Arg Lys Lys Arg Lys Gln Lys Glu Gln Ser Gly Gly 500 505 510 Glu Glu Lys Asp Glu Asp Glu Phe Gln Lys Ser Glu Ser Glu Asp Ser 515 520 525 Ile Arg Arg Lys Gly Phe Arg Phe Ser Ile Glu Gly Asn Arg Leu Thr 530 535 540 Tyr Glu Lys Arg Tyr Ser Ser Pro His Gln Ser Leu Leu Ser Ile Arg 545 550 555 560 Gly Ser Leu Phe Ser Pro Arg Arg Asn Ser Arg Thr Ser Leu Phe Ser 565 570 575 Phe Arg Gly Arg Ala Lys Asp Val Gly Ser Glu Asn Asp Phe Ala Asp 580 585 590 Asp Glu His Ser Thr Phe Glu Asp Asn Glu Ser Arg Arg Asp Ser Leu 595 600 605 Phe Val Pro Arg Arg His Gly Glu Arg Arg Asn Ser Asn Leu Ser Gln 610 615 620 Thr Ser Arg Ser Ser Arg Met Leu Ala Val Phe Pro Ala Asn Gly Lys 625 630 635 640 Met His Ser Thr Val Asp Cys Asn Gly Val Val Ser Leu Val Gly Gly 645 650 655 Pro Ser Val Pro Thr Ser Pro Val Gly Gln Leu Leu Pro Glu Gly Thr 660 665 670 Thr Thr Glu Thr Glu Met Arg Lys Arg Arg Ser Ser Ser Phe His Val 675 680 685 Ser Met Asp Phe Leu Glu Asp Pro Ser Gln Arg Gln Arg Ala Met Ser 690 695 700 Ile Ala Ser Ile Leu Thr Asn Thr Val Glu Glu Leu Glu Glu Ser Arg 705 710 715 720 Gln Lys Cys Pro Pro Cys Trp Tyr Lys Phe Ser Asn Ile Phe Leu Ile 725 730 735 Trp Asp Cys Ser Pro Tyr Trp Leu Lys Val Lys His Val Val Asn Leu 740 745 750 Val Val Met Asp Pro Phe Val Asp Leu Ala Ile Thr Ile Cys Ile Val 755 760 765 Leu Asn Thr Leu Phe Met Ala Met Glu His Tyr Pro Met Thr Asp His 770 775 780 Phe Asn Asn Val Leu Thr Val Gly Asn Leu Val Phe Thr Gly Ile Phe 785 790 795 800 Thr Ala Glu Met Phe Leu Lys Ile Ile Ala Met Asp Pro Tyr Tyr Tyr 805 810 815 Phe Gln Glu Gly Trp Asn Ile Phe Asp Gly Phe Ile Val Thr Leu Ser 820 825 830 Leu Val Glu Leu Gly Leu Ala Asn Val Glu Gly Leu Ser Val Leu Arg 835 840 845 Ser Phe Arg Leu Leu Arg Val Phe Lys Leu Ala Lys Ser Trp Pro Thr 850 855 860 Leu Asn Met Leu Ile Lys Ile Ile Gly Asn Ser Val Gly Ala Leu Gly 865 870 875 880 Asn Leu Thr Leu Val Leu Ala Ile Ile Val Phe Ile Phe Ala Val Val 885 890 895 Gly Met Gln Leu Phe Gly Lys Ser Tyr Lys Asp Cys Val Cys Lys Ile 900 905 910 Ala Ser Asp Cys Gln Leu Pro Arg Trp His Met Asn Asp Phe Phe His 915 920 925 Ser Phe Leu Ile Val Phe Arg Val Leu Cys Gly Glu Trp Ile Glu Thr 930 935 940 Met Trp Asp Cys Met Glu Val Ala Gly Gln Ala Met Cys Leu Thr Val 945 950 955 960 Phe Met Met Val Met Val Ile Gly Asn Leu Val Val Leu Asn Leu Phe 965 970 975 Leu Ala Leu Leu Xaa Ser Ser Phe Ser Ala Asp Asn Leu Ala Ala Thr 980 985 990 Asp Asp Asp Asn Glu Met Asn Asn Leu Gln Ile Ala Val Asp Arg Met 995 1000 1005 His Lys Gly Val Ala Tyr Val Lys Arg Lys Ile Tyr Glu Phe Ile Gln 1010 1015 1020 Gln Ser Phe Ile Arg Lys Gln Lys Ile Leu Asp Glu Ile Lys Pro Leu 1025 1030 1035 1040 Asp Asp Leu Asn Asn Lys Lys Asp Ser Cys Met Ser Asn His Thr Xaa 1045 1050 1055 Glu Ile Gly Lys Asp Leu Asp Tyr Leu Lys Asp Val Asn Gly Thr Thr 1060 1065 1070 Ser Gly Ile Gly Thr Gly Ser Ser Val Glu Lys Tyr Ile Ile Asp Glu 1075 1080 1085 Ser Asp Tyr Met Ser Phe Ile Asn Asn Pro Ser Leu Thr Val Thr Val 1090 1095 1100 Pro Ile Ala Val Gly Glu Ser Asp Phe Glu Asn Leu Asn Thr Glu Asp 1105 1110 1115 1120 Phe Ser Ser Glu Ser Asp Leu Glu Glu Ser Lys Glu Lys Leu Asn Glu 1125 1130 1135 Ser Ser Ser Ser Ser Glu Gly Ser Thr Val Asp Ile Gly Ala Pro Val 1140 1145 1150 Glu Glu Gln Pro Val Val Glu Pro Glu Glu Thr Leu Glu Pro Glu Ala 1155 1160 1165 Cys Phe Thr Glu Gly Cys Val Gln Arg Phe Lys Cys Cys Gln Ile Asn 1170 1175 1180 Val Glu Glu Gly Arg Gly Lys Gln Trp Trp Asn Leu Arg Arg Thr Cys 1185 1190 1195 1200 Phe Arg Ile Val Glu His Asn Trp Phe Glu Thr Phe Ile Val Phe Met 1205 1210 1215 Ile Leu Leu Ser Ser Gly Ala Leu Ala Phe Glu Asp Ile Tyr Ile Asp 1220 1225 1230 Gln Arg Lys Thr Ile Lys Thr Met Leu Glu Tyr Ala Asp Lys Val Phe 1235 1240 1245 Thr Tyr Ile Phe Ile Leu Glu Met Leu Leu Lys Trp Val Ala Tyr Gly 1250 1255 1260 Tyr Gln Thr Tyr Phe Thr Asn Ala Trp Cys Trp Leu Asp Phe Leu Ile 1265 1270 1275 1280 Val Asp Val Ser Leu Val Ser Leu Thr Ala Asn Ala Leu Gly Tyr Ser 1285 1290 1295 Glu Leu Gly Ala Ile Lys Ser Leu Arg Thr Leu Arg Ala Leu Arg Pro 1300 1305 1310 Leu Arg Ala Leu Ser Arg Phe Glu Gly Met Arg Asp Asn Leu Ala Pro 1315 1320 1325 Thr Trp Met Gly Trp Ser Ala Gly Ser Ser Pro Glu Pro Phe Ile Met 1330 1335 1340 Gly Gly Cys Glu Cys Pro Phe Arg Ser Asn Ser Ile His His Glu Cys 1345 1350 1355 1360 Ala Ser Gly Leu Ser Tyr Ile Leu Ala Asn Phe Gln His His Gly Arg 1365 1370 1375 Lys Phe Val Cys Trp Gln Ile Leu Pro Leu Tyr 1380 1385 11 6030 DNA homo sapiens 11 atggagcaaa cagtgcttgt accaccagga cctgacagct tcaacttctt caccagagaa 60 tctcttgcgg ctattgaaag acgcattgca gaagaaaagg caaagaatcc caaaccagac 120 aaaaaagatg acgacgaaaa tggcccaaag ccaaatagtg acttggaagc tggaaagaac 180 cttccattta tttatggaga cattcctcca gagatggtgt cagagcccct ggaggacctg 240 gacccctact atatcaataa gaaaactttt atagtattga ataaagggaa ggccatcttc 300 cggttcagtg ccacctctgc cctgtacatt ttaactccct tcaatcctct taggaaaata 360 gctattaaga ttttggtaca ttcattattc agcatgctaa ttatgtgcac tattttgaca 420 aactgtgtgt ttatgacaat gagtaaccct cctgattgga caaagaatgt agaatacacc 480 ttcacaggaa tatatacttt tgaatcactt ataaaaatta ttgcaagggg attctgttta 540 gaagatttta ctttccttcg ggatccatgg aactggctcg atttcactgt cattacattt 600 gcgtacgtca cagagtttgt ggacctgggc aatgtctcgg cattgagaac attcagagtt 660 ctccgagcat tgaagacgat ttcagtcatt ccaggcctga aaaccattgt gggagccctg 720 atccagtctg tgaagaagct ctcagatgta atgatcctga ctgtgttctg tctgagcgta 780 tttgctctaa ttgggctgca gctgttcatg ggcaacctga ggaataaatg tatacaatgg 840 cctcccacca atgcttcctt ggaggaacat agtatagaaa agaatataac tgtgaattat 900 aatggtacac ttataaatga aactgtcttt gagtttgact ggaagtcata tattcaagat 960 tcaagatatc attatttcct ggagggtttt ttagatgcac tactatgtgg aaatagctct 1020 gatgcaggcc aatgtccaga gggatatatg tgtgtgaaag ctggtagaaa tcccaattat 1080 ggctacacaa gctttgatac cttcagttgg gcttttttgt ccttgtttcg actaatgact 1140 caggacttct gggaaaatct ttatcaactg acattacgtg ctgctgggaa aacgtacatg 1200 atattttttg tgttggtcat tttcttgggc tcattctacc taataaattt gatcctggct 1260 gtggtggcca tggcctacga ggaacagaat caggccacct tggaagaagc agaacagaaa 1320 gaggccgaat ttcagcagat gattgaacag cttaaaaagc aacaggaggc agctcagcag 1380 gcagcaacgg caactgcctc agaacattcc agagagccca gtgcagcagg caggctctca 1440 gacagctcat ctgaagcctc taagttgagt tccaagagtg ctaaggaaag aagaaatcgg 1500 aggaagaaaa gaaaacagaa agagcagtct ggtggggaag agaaagatga ggatgaattc 1560 caaaaatctg aatctgagga cagcatcagg aggaaaggtt ttcgcttctc cattgaaggg 1620 aaccgattga catatgaaaa gaggtactcc tccccacacc agtctttgtt gagcatccgt 1680 ggctccctat tttcaccaag gcgaaatagc agaacaagcc ttttcagctt tagagggcga 1740 gcaaaggatg tgggatctga gaacgacttc gcagatgatg agcacagcac ctttgaggat 1800 aacgagagcc gtagagattc cttgtttgtg ccccgacgac acggagagag acgcaacagc 1860 aacctgagtc agaccagtag gtcatcccgg atgctggcag tgtttccagc gaatgggaag 1920 atgcacagca ctgtggattg caatggtgtg gtttccttgg ttggtggacc ttcagttcct 1980 acatcgcctg ttggacagct tctgccagag gtgataatag ataagccagc tactgatgac 2040 aatggaacaa ccactgaaac tgaaatgaga aagagaaggt caagttcttt ccacgtttcc 2100 atggactttc tagaagatcc ttcccaaagg caacgagcaa tgagtatagc cagcattcta 2160 acaaatacag tagaagaact tgaagaatcc aggcagaaat gcccaccctg ttggtataaa 2220 ttttccaaca tattcttaat ctgggactgt tctccatatt ggttaaaagt gaaacatgtt 2280 gtcaacctgg tygtgatgga cccatttgtt gacctggcca tcaccatctg tattgtctta 2340 aatactcttt tcatggccat ggagcactat ccaatgacgg accatttcaa taatgtgctt 2400 acagtaggaa acttggtttt cactgggatc tttacagcag aaatgtttct gaaaattatt 2460 gccatggatc cttactatta tttccaagaa ggctggaata tctttgacgg ttttattgtg 2520 acgcttagcc tggtagaact tggactcgcc aatgtggaag gattatctgt tctccgttca 2580 tttcgattgc tgcgagtttt caagttggca aaatcttggc caacgttaaa tatgctaata 2640 aagatcatcg gcaattccgt gggggctctg ggaaatttaa ccctcgtctt ggccatcatc 2700 gtcttcattt ttgccgtggt cggcatgcag ctctttggta aaagctacaa agattgtgtc 2760 tgcaagatcg ccagtgattg tcaactccca cgctggcaca tgaatgactt cttccactcc 2820 ttcctgattg tgttccgcgt gctgtgtggg gagtggatag agaccatgtg ggactgtatg 2880 gaggttgctg gtcaagccat gtgccttact gtcttcatga tggtcatggt gattggaaac 2940 ctagtggtcc tgaatctctt tctggccttg cttmtgagct catttagtgc agacaacctt 3000 gcagccactg atgatgataa tgaaatgaat aatctccaaa ttgctgtgga taggatgcac 3060 aaaggagtag cttatgtgaa aagaaaaata tatgaattta ttcaacagtc cttcattagg 3120 aaacaaaaga ttttagatga aattaaacca cttgatgatc taaacaacaa gaaagacagt 3180 tgtatgtcca atcatacarc agaaattggg aaagatcttg actatcttaa agatgtaaat 3240 ggaactacaa gtggtatagg aactggcagc agtgttgaaa aatacattat tgatgaaagt 3300 gattacatgt cattcataaa caaccccagt cttactgtga ctgtaccaat tgctgtagga 3360 gaatctgact ttgaaaattt aaacacggaa gactttagta gtgaatcgga tctggaagaa 3420 agcaaagaga aactgaatga aagcagtagc tcatcagaag gtagcactgt ggacatcggc 3480 gcacctgtag aagaacagcc cgtagtggaa cctgaagaaa ctcttgaacc agaagcttgt 3540 ttcactgaag gctgtgtaca aagattcaag tgttgtcaaa tcaatgtgga agaaggcaga 3600 ggaaaacaat ggtggaacct gagaaggacg tgtttccgaa tagttgaaca taactggttt 3660 gagaccttca ttgttttcat gattctcctt agtagtggtg ctctggcatt tgaagatata 3720 tatattgatc agcgaaagac gattaagacg atgttggaat atgctgacaa ggttttcact 3780 tacattttca ttctggaaat gcttctaaaa tgggtggcat atggctatca aacatatttc 3840 accaatgcct ggtgttggct ggacttctta attgttgatg tttcattggt cagtttaaca 3900 gcaaatgcct tgggttactc agaacttgga gccatcaaat ctctcaggac actaagagct 3960 ctgagacctc taagagcctt atctcgattt gaagggatga gggtggttgt gaatgccctt 4020 ttaggagcaa ttccatccat catgaatgtg cttctggttt gtcttatatt ctggctaatt 4080 ttcagcatca tgggcgtaaa tttgtttgct ggcaaattct accactgtat taacaccaca 4140 actggtgaca ggtttgacat cgaagacgtg aataatcata ctgattgcct aaaactaata 4200 gaaagaaatg agactgctcg atggaaaaat gtgaaagtaa actttgataa tgtaggattt 4260 gggtatctct ctttgcttca agttgccaca ttcaaaggat ggatggatat aatgtatgca 4320 gcagttgatt ccagaaatgt ggaactccag cctaagtatg aagaaagtct gtacatgtat 4380 ctttactttg ttattttcat catctttggg tccttcttca ccttgaacct gtttattggt 4440 gtcatcatag ataatttcaa ccagcagaaa aagaagtttg gaggtcaaga catctttatg 4500 acagaagaac agaagaaata ctataatgca atgaaaaaat taggatcgaa aaaaccgcaa 4560 aagcctatac ctcgaccagg aaacaaattt caaggaatgg tctttgactt cgtaaccaga 4620 caagtttttg acataagcat catgattctc atctgtctta acatggtcac aatgatggtg 4680 gaaacagatg accagagtga atatgtgact accattttgt cacgcatcaa tctggtgttc 4740 attgtgctat ttactggaga gtgtgtactg aaactcatct ctctacgcca ttattatttt 4800 accattggat ggaatatttt tgattttgtg gttgtcattc tctccattgt aggtatgttt 4860 cttgccgagc tgatagaaaa gtatttcgtg tcccctaccc tgttccgagt gatccgtctt 4920 gctaggattg gccgaatcct acgtctgatc aaaggagcaa aggggatccg cacgctgctc 4980 tttgctttga tgatgtccct tcctgcgttg tttaacatcg gcctcctact cttcctagtc 5040 atgttcatct acgccatctt tgggatgtcc aactttgcct atgttaagag ggaagttggg 5100 atcgatgaca tgttcaactt tgagaccttt ggcaacagca tgatctgcct attccaaatt 5160 acaacctctg ctggctggga tggattgcta gcacccattc tcaacagtaa gccacccgac 5220 tgtgacccta ataaagttaa ccctggaagc tcagttaagg gagactgtgg gaacccatct 5280 gttggaattt tcttttttgt cagttacatc atcatatcct tcctggttgt ggtgaacatg 5340 tacatcgcgg tcatcctgga gaacttcagt gttgctactg aagaaagtgc agagcctctg 5400 agtgaggatg actttgagat gttctatgag gtttgggaga agtttgatcc cgatgcaact 5460 cagttcatgg aatttgaaaa attatctcag tttgcagctg cgcttgaacc gcctctcaat 5520 ctgccacaac caaacaaact ccagctcatt gccatggatt tgcccatggt gagtggtgac 5580 cggatccact gtcttgatat cttatttgct tttacaaagc gggttctagg agagagtgga 5640 gagatggatg ctctacgaat acagatggaa gagcgattca tggcttccaa tccttccaag 5700 gtctcctatc agccaatcac tactacttta aaacgaaaac aagaggaagt atctgctgtc 5760 attattcagc gtgcttacag acgccacctt ttaaagcgaa ctgtaaaaca agcttccttt 5820 acgtacaata aaaacaaaat caaaggtggg gctaatcttc ttataaaaga agacatgata 5880 attgacagaa taaatgaaaa ctctattaca gaaaaaactg atctgaccat gtccactgca 5940 gcttgtccac cttcctatga ccgggtgaca aagccaattg tggaaaaaca tgagcaagaa 6000 ggcaaagatg aaaaagccaa agggaaataa 6030 12 2009 PRT homo sapiens VARIANT (1)...(2009) Xaa = Any Amino Acid 12 Met Glu Gln Thr Val Leu Val Pro Pro Gly Pro Asp Ser Phe Asn Phe 1 5 10 15 Phe Thr Arg Glu Ser Leu Ala Ala Ile Glu Arg Arg Ile Ala Glu Glu 20 25 30 Lys Ala Lys Asn Pro Lys Pro Asp Lys Lys Asp Asp Asp Glu Asn Gly 35 40 45 Pro Lys Pro Asn Ser Asp Leu Glu Ala Gly Lys Asn Leu Pro Phe Ile 50 55 60 Tyr Gly Asp Ile Pro Pro Glu Met Val Ser Glu Pro Leu Glu Asp Leu 65 70 75 80 Asp Pro Tyr Tyr Ile Asn Lys Lys Thr Phe Ile Val Leu Asn Lys Gly 85 90 95 Lys Ala Ile Phe Arg Phe Ser Ala Thr Ser Ala Leu Tyr Ile Leu Thr 100 105 110 Pro Phe Asn Pro Leu Arg Lys Ile Ala Ile Lys Ile Leu Val His Ser 115 120 125 Leu Phe Ser Met Leu Ile Met Cys Thr Ile Leu Thr Asn Cys Val Phe 130 135 140 Met Thr Met Ser Asn Pro Pro Asp Trp Thr Lys Asn Val Glu Tyr Thr 145 150 155 160 Phe Thr Gly Ile Tyr Thr Phe Glu Ser Leu Ile Lys Ile Ile Ala Arg 165 170 175 Gly Phe Cys Leu Glu Asp Phe Thr Phe Leu Arg Asp Pro Trp Asn Trp 180 185 190 Leu Asp Phe Thr Val Ile Thr Phe Ala Tyr Val Thr Glu Phe Val Asp 195 200 205 Leu Gly Asn Val Ser Ala Leu Arg Thr Phe Arg Val Leu Arg Ala Leu 210 215 220 Lys Thr Ile Ser Val Ile Pro Gly Leu Lys Thr Ile Val Gly Ala Leu 225 230 235 240 Ile Gln Ser Val Lys Lys Leu Ser Asp Val Met Ile Leu Thr Val Phe 245 250 255 Cys Leu Ser Val Phe Ala Leu Ile Gly Leu Gln Leu Phe Met Gly Asn 260 265 270 Leu Arg Asn Lys Cys Ile Gln Trp Pro Pro Thr Asn Ala Ser Leu Glu 275 280 285 Glu His Ser Ile Glu Lys Asn Ile Thr Val Asn Tyr Asn Gly Thr Leu 290 295 300 Ile Asn Glu Thr Val Phe Glu Phe Asp Trp Lys Ser Tyr Ile Gln Asp 305 310 315 320 Ser Arg Tyr His Tyr Phe Leu Glu Gly Phe Leu Asp Ala Leu Leu Cys 325 330 335 Gly Asn Ser Ser Asp Ala Gly Gln Cys Pro Glu Gly Tyr Met Cys Val 340 345 350 Lys Ala Gly Arg Asn Pro Asn Tyr Gly Tyr Thr Ser Phe Asp Thr Phe 355 360 365 Ser Trp Ala Phe Leu Ser Leu Phe Arg Leu Met Thr Gln Asp Phe Trp 370 375 380 Glu Asn Leu Tyr Gln Leu Thr Leu Arg Ala Ala Gly Lys Thr Tyr Met 385 390 395 400 Ile Phe Phe Val Leu Val Ile Phe Leu Gly Ser Phe Tyr Leu Ile Asn 405 410 415 Leu Ile Leu Ala Val Val Ala Met Ala Tyr Glu Glu Gln Asn Gln Ala 420 425 430 Thr Leu Glu Glu Ala Glu Gln Lys Glu Ala Glu Phe Gln Gln Met Ile 435 440 445 Glu Gln Leu Lys Lys Gln Gln Glu Ala Ala Gln Gln Ala Ala Thr Ala 450 455 460 Thr Ala Ser Glu His Ser Arg Glu Pro Ser Ala Ala Gly Arg Leu Ser 465 470 475 480 Asp Ser Ser Ser Glu Ala Ser Lys Leu Ser Ser Lys Ser Ala Lys Glu 485 490 495 Arg Arg Asn Arg Arg Lys Lys Arg Lys Gln Lys Glu Gln Ser Gly Gly 500 505 510 Glu Glu Lys Asp Glu Asp Glu Phe Gln Lys Ser Glu Ser Glu Asp Ser 515 520 525 Ile Arg Arg Lys Gly Phe Arg Phe Ser Ile Glu Gly Asn Arg Leu Thr 530 535 540 Tyr Glu Lys Arg Tyr Ser Ser Pro His Gln Ser Leu Leu Ser Ile Arg 545 550 555 560 Gly Ser Leu Phe Ser Pro Arg Arg Asn Ser Arg Thr Ser Leu Phe Ser 565 570 575 Phe Arg Gly Arg Ala Lys Asp Val Gly Ser Glu Asn Asp Phe Ala Asp 580 585 590 Asp Glu His Ser Thr Phe Glu Asp Asn Glu Ser Arg Arg Asp Ser Leu 595 600 605 Phe Val Pro Arg Arg His Gly Glu Arg Arg Asn Ser Asn Leu Ser Gln 610 615 620 Thr Ser Arg Ser Ser Arg Met Leu Ala Val Phe Pro Ala Asn Gly Lys 625 630 635 640 Met His Ser Thr Val Asp Cys Asn Gly Val Val Ser Leu Val Gly Gly 645 650 655 Pro Ser Val Pro Thr Ser Pro Val Gly Gln Leu Leu Pro Glu Val Ile 660 665 670 Ile Asp Lys Pro Ala Thr Asp Asp Asn Gly Thr Thr Thr Glu Thr Glu 675 680 685 Met Arg Lys Arg Arg Ser Ser Ser Phe His Val Ser Met Asp Phe Leu 690 695 700 Glu Asp Pro Ser Gln Arg Gln Arg Ala Met Ser Ile Ala Ser Ile Leu 705 710 715 720 Thr Asn Thr Val Glu Glu Leu Glu Glu Ser Arg Gln Lys Cys Pro Pro 725 730 735 Cys Trp Tyr Lys Phe Ser Asn Ile Phe Leu Ile Trp Asp Cys Ser Pro 740 745 750 Tyr Trp Leu Lys Val Lys His Val Val Asn Leu Val Val Met Asp Pro 755 760 765 Phe Val Asp Leu Ala Ile Thr Ile Cys Ile Val Leu Asn Thr Leu Phe 770 775 780 Met Ala Met Glu His Tyr Pro Met Thr Asp His Phe Asn Asn Val Leu 785 790 795 800 Thr Val Gly Asn Leu Val Phe Thr Gly Ile Phe Thr Ala Glu Met Phe 805 810 815 Leu Lys Ile Ile Ala Met Asp Pro Tyr Tyr Tyr Phe Gln Glu Gly Trp 820 825 830 Asn Ile Phe Asp Gly Phe Ile Val Thr Leu Ser Leu Val Glu Leu Gly 835 840 845 Leu Ala Asn Val Glu Gly Leu Ser Val Leu Arg Ser Phe Arg Leu Leu 850 855 860 Arg Val Phe Lys Leu Ala Lys Ser Trp Pro Thr Leu Asn Met Leu Ile 865 870 875 880 Lys Ile Ile Gly Asn Ser Val Gly Ala Leu Gly Asn Leu Thr Leu Val 885 890 895 Leu Ala Ile Ile Val Phe Ile Phe Ala Val Val Gly Met Gln Leu Phe 900 905 910 Gly Lys Ser Tyr Lys Asp Cys Val Cys Lys Ile Ala Ser Asp Cys Gln 915 920 925 Leu Pro Arg Trp His Met Asn Asp Phe Phe His Ser Phe Leu Ile Val 930 935 940 Phe Arg Val Leu Cys Gly Glu Trp Ile Glu Thr Met Trp Asp Cys Met 945 950 955 960 Glu Val Ala Gly Gln Ala Met Cys Leu Thr Val Phe Met Met Val Met 965 970 975 Val Ile Gly Asn Leu Val Val Leu Asn Leu Phe Leu Ala Leu Leu Xaa 980 985 990 Ser Ser Phe Ser Ala Asp Asn Leu Ala Ala Thr Asp Asp Asp Asn Glu 995 1000 1005 Met Asn Asn Leu Gln Ile Ala Val Asp Arg Met His Lys Gly Val Ala 1010 1015 1020 Tyr Val Lys Arg Lys Ile Tyr Glu Phe Ile Gln Gln Ser Phe Ile Arg 1025 1030 1035 1040 Lys Gln Lys Ile Leu Asp Glu Ile Lys Pro Leu Asp Asp Leu Asn Asn 1045 1050 1055 Lys Lys Asp Ser Cys Met Ser Asn His Thr Xaa Glu Ile Gly Lys Asp 1060 1065 1070 Leu Asp Tyr Leu Lys Asp Val Asn Gly Thr Thr Ser Gly Ile Gly Thr 1075 1080 1085 Gly Ser Ser Val Glu Lys Tyr Ile Ile Asp Glu Ser Asp Tyr Met Ser 1090 1095 1100 Phe Ile Asn Asn Pro Ser Leu Thr Val Thr Val Pro Ile Ala Val Gly 1105 1110 1115 1120 Glu Ser Asp Phe Glu Asn Leu Asn Thr Glu Asp Phe Ser Ser Glu Ser 1125 1130 1135 Asp Leu Glu Glu Ser Lys Glu Lys Leu Asn Glu Ser Ser Ser Ser Ser 1140 1145 1150 Glu Gly Ser Thr Val Asp Ile Gly Ala Pro Val Glu Glu Gln Pro Val 1155 1160 1165 Val Glu Pro Glu Glu Thr Leu Glu Pro Glu Ala Cys Phe Thr Glu Gly 1170 1175 1180 Cys Val Gln Arg Phe Lys Cys Cys Gln Ile Asn Val Glu Glu Gly Arg 1185 1190 1195 1200 Gly Lys Gln Trp Trp Asn Leu Arg Arg Thr Cys Phe Arg Ile Val Glu 1205 1210 1215 His Asn Trp Phe Glu Thr Phe Ile Val Phe Met Ile Leu Leu Ser Ser 1220 1225 1230 Gly Ala Leu Ala Phe Glu Asp Ile Tyr Ile Asp Gln Arg Lys Thr Ile 1235 1240 1245 Lys Thr Met Leu Glu Tyr Ala Asp Lys Val Phe Thr Tyr Ile Phe Ile 1250 1255 1260 Leu Glu Met Leu Leu Lys Trp Val Ala Tyr Gly Tyr Gln Thr Tyr Phe 1265 1270 1275 1280 Thr Asn Ala Trp Cys Trp Leu Asp Phe Leu Ile Val Asp Val Ser Leu 1285 1290 1295 Val Ser Leu Thr Ala Asn Ala Leu Gly Tyr Ser Glu Leu Gly Ala Ile 1300 1305 1310 Lys Ser Leu Arg Thr Leu Arg Ala Leu Arg Pro Leu Arg Ala Leu Ser 1315 1320 1325 Arg Phe Glu Gly Met Arg Val Val Val Asn Ala Leu Leu Gly Ala Ile 1330 1335 1340 Pro Ser Ile Met Asn Val Leu Leu Val Cys Leu Ile Phe Trp Leu Ile 1345 1350 1355 1360 Phe Ser Ile Met Gly Val Asn Leu Phe Ala Gly Lys Phe Tyr His Cys 1365 1370 1375 Ile Asn Thr Thr Thr Gly Asp Arg Phe Asp Ile Glu Asp Val Asn Asn 1380 1385 1390 His Thr Asp Cys Leu Lys Leu Ile Glu Arg Asn Glu Thr Ala Arg Trp 1395 1400 1405 Lys Asn Val Lys Val Asn Phe Asp Asn Val Gly Phe Gly Tyr Leu Ser 1410 1415 1420 Leu Leu Gln Val Ala Thr Phe Lys Gly Trp Met Asp Ile Met Tyr Ala 1425 1430 1435 1440 Ala Val Asp Ser Arg Asn Val Glu Leu Gln Pro Lys Tyr Glu Glu Ser 1445 1450 1455 Leu Tyr Met Tyr Leu Tyr Phe Val Ile Phe Ile Ile Phe Gly Ser Phe 1460 1465 1470 Phe Thr Leu Asn Leu Phe Ile Gly Val Ile Ile Asp Asn Phe Asn Gln 1475 1480 1485 Gln Lys Lys Lys Phe Gly Gly Gln Asp Ile Phe Met Thr Glu Glu Gln 1490 1495 1500 Lys Lys Tyr Tyr Asn Ala Met Lys Lys Leu Gly Ser Lys Lys Pro Gln 1505 1510 1515 1520 Lys Pro Ile Pro Arg Pro Gly Asn Lys Phe Gln Gly Met Val Phe Asp 1525 1530 1535 Phe Val Thr Arg Gln Val Phe Asp Ile Ser Ile Met Ile Leu Ile Cys 1540 1545 1550 Leu Asn Met Val Thr Met Met Val Glu Thr Asp Asp Gln Ser Glu Tyr 1555 1560 1565 Val Thr Thr Ile Leu Ser Arg Ile Asn Leu Val Phe Ile Val Leu Phe 1570 1575 1580 Thr Gly Glu Cys Val Leu Lys Leu Ile Ser Leu Arg His Tyr Tyr Phe 1585 1590 1595 1600 Thr Ile Gly Trp Asn Ile Phe Asp Phe Val Val Val Ile Leu Ser Ile 1605 1610 1615 Val Gly Met Phe Leu Ala Glu Leu Ile Glu Lys Tyr Phe Val Ser Pro 1620 1625 1630 Thr Leu Phe Arg Val Ile Arg Leu Ala Arg Ile Gly Arg Ile Leu Arg 1635 1640 1645 Leu Ile Lys Gly Ala Lys Gly Ile Arg Thr Leu Leu Phe Ala Leu Met 1650 1655 1660 Met Ser Leu Pro Ala Leu Phe Asn Ile Gly Leu Leu Leu Phe Leu Val 1665 1670 1675 1680 Met Phe Ile Tyr Ala Ile Phe Gly Met Ser Asn Phe Ala Tyr Val Lys 1685 1690 1695 Arg Glu Val Gly Ile Asp Asp Met Phe Asn Phe Glu Thr Phe Gly Asn 1700 1705 1710 Ser Met Ile Cys Leu Phe Gln Ile Thr Thr Ser Ala Gly Trp Asp Gly 1715 1720 1725 Leu Leu Ala Pro Ile Leu Asn Ser Lys Pro Pro Asp Cys Asp Pro Asn 1730 1735 1740 Lys Val Asn Pro Gly Ser Ser Val Lys Gly Asp Cys Gly Asn Pro Ser 1745 1750 1755 1760 Val Gly Ile Phe Phe Phe Val Ser Tyr Ile Ile Ile Ser Phe Leu Val 1765 1770 1775 Val Val Asn Met Tyr Ile Ala Val Ile Leu Glu Asn Phe Ser Val Ala 1780 1785 1790 Thr Glu Glu Ser Ala Glu Pro Leu Ser Glu Asp Asp Phe Glu Met Phe 1795 1800 1805 Tyr Glu Val Trp Glu Lys Phe Asp Pro Asp Ala Thr Gln Phe Met Glu 1810 1815 1820 Phe Glu Lys Leu Ser Gln Phe Ala Ala Ala Leu Glu Pro Pro Leu Asn 1825 1830 1835 1840 Leu Pro Gln Pro Asn Lys Leu Gln Leu Ile Ala Met Asp Leu Pro Met 1845 1850 1855 Val Ser Gly Asp Arg Ile His Cys Leu Asp Ile Leu Phe Ala Phe Thr 1860 1865 1870 Lys Arg Val Leu Gly Glu Ser Gly Glu Met Asp Ala Leu Arg Ile Gln 1875 1880 1885 Met Glu Glu Arg Phe Met Ala Ser Asn Pro Ser Lys Val Ser Tyr Gln 1890 1895 1900 Pro Ile Thr Thr Thr Leu Lys Arg Lys Gln Glu Glu Val Ser Ala Val 1905 1910 1915 1920 Ile Ile Gln Arg Ala Tyr Arg Arg His Leu Leu Lys Arg Thr Val Lys 1925 1930 1935 Gln Ala Ser Phe Thr Tyr Asn Lys Asn Lys Ile Lys Gly Gly Ala Asn 1940 1945 1950 Leu Leu Ile Lys Glu Asp Met Ile Ile Asp Arg Ile Asn Glu Asn Ser 1955 1960 1965 Ile Thr Glu Lys Thr Asp Leu Thr Met Ser Thr Ala Ala Cys Pro Pro 1970 1975 1980 Ser Tyr Asp Arg Val Thr Lys Pro Ile Val Glu Lys His Glu Gln Glu 1985 1990 1995 2000 Gly Lys Asp Glu Lys Ala Lys Gly Lys 2005 13 5922 DNA homo sapiens 13 atggagcaaa cagtgcttgt accaccagga cctgacagct tcaacttctt caccagagaa 60 tctcttgcgg ctattgaaag acgcattgca gaagaaaagg caaagaatcc caaaccagac 120 aaaaaagatg acgacgaaaa tggcccaaag ccaaatagtg acttggaagc tggaaagaac 180 cttccattta tttatggaga cattcctcca gagatggtgt cagagcccct ggaggacctg 240 gacccctact atatcaataa gaaaactttt atagtattga ataaagggaa ggccatcttc 300 cggttcagtg ccacctctgc cctgtacatt ttaactccct tcaatcctct taggaaaata 360 gctattaaga ttttggtaca ttcattattc agcatgctaa ttatgtgcac tattttgaca 420 aactgtgtgt ttatgacaat gagtaaccct cctgattgga caaagaatgt agaatacacc 480 ttcacaggaa tatatacttt tgaatcactt ataaaaatta ttgcaagggg attctgttta 540 gaagatttta ctttccttcg ggatccatgg aactggctcg atttcactgt cattacattt 600 gcgtacgtca cagagtttgt ggacctgggc aatgtctcgg cattgagaac attcagagtt 660 ctccgagcat tgaagacgat ttcagtcatt ccaggcctga aaaccattgt gggagccctg 720 atccagtctg tgaagaagct ctcagatgta atgatcctga ctgtgttctg tctgagcgta 780 tttgctctaa ttgggctgca gctgttcatg ggcaacctga ggaataaatg tatacaatgg 840 cctcccacca atgcttcctt ggaggaacat agtatagaaa agaatataac tgtgaattat 900 aatggtacac ttataaatga aactgtcttt gagtttgact ggaagtcata tattcaagat 960 tcaagatatc attatttcct ggagggtttt ttagatgcac tactatgtgg aaatagctct 1020 gatgcaggcc aatgtccaga gggatatatg tgtgtgaaag ctggtagaaa tcccaattat 1080 ggctacacaa gctttgatac cttcagttgg gcttttttgt ccttgtttcg actaatgact 1140 caggacttct gggaaaatct ttatcaactg acattacgtg ctgctgggaa aacgtacatg 1200 atattttttg tgttggtcat tttcttgggc tcattctacc taataaattt gatcctggct 1260 gtggtggcca tggcctacga ggaacagaat caggccacct tggaagaagc agaacagaaa 1320 gaggccgaat ttcagcagat gattgaacag cttaaaaagc aacaggaggc agctcagcag 1380 gcagcaacgg caactgcctc agaacattcc agagagccca gtgcagcagg caggctctca 1440 gacagctcat ctgaagcctc taagttgagt tccaagagtg ctaaggaaag aagaaatcgg 1500 aggaagaaaa gaaaacagaa agagcagtct ggtggggaag agaaagatga ggatgaattc 1560 caaaaatctg aatctgagga cagcatcagg aggaaaggtt ttcgcttctc cattgaaggg 1620 aaccgattga catatgaaaa gaggtactcc tccccacacc agtctttgtt gagcatccgt 1680 ggctccctat tttcaccaag gcgaaatagc agaacaagcc ttttcagctt tagagggcga 1740 gcaaaggatg tgggatctga gaacgacttc gcagatgatg agcacagcac ctttgaggat 1800 aacgagagcc gtagagattc cttgtttgtg ccccgacgac acggagagag acgcaacagc 1860 aacctgagtc agaccagtag gtcatcccgg atgctggcag tgtttccagc gaatgggaag 1920 atgcacagca ctgtggattg caatggtgtg gtttccttgg ttggtggacc ttcagttcct 1980 acatcgcctg ttggacagct tctgccagag gtgataatag ataagccagc tactgatgac 2040 aatggaacaa ccactgaaac tgaaatgaga aagagaaggt caagttcttt ccacgtttcc 2100 atggactttc tagaagatcc ttcccaaagg caacgagcaa tgagtatagc cagcattcta 2160 acaaatacag tagaagaact tgaagaatcc aggcagaaat gcccaccctg ttggtataaa 2220 ttttccaaca tattcttaat ctgggactgt tctccatatt ggttaaaagt gaaacatgtt 2280 gtcaacctgg tygtgatgga cccatttgtt gacctggcca tcaccatctg tattgtctta 2340 aatactcttt tcatggccat ggagcactat ccaatgacgg accatttcaa taatgtgctt 2400 acagtaggaa acttggtttt cactgggatc tttacagcag aaatgtttct gaaaattatt 2460 gccatggatc cttactatta tttccaagaa ggctggaata tctttgacgg ttttattgtg 2520 acgcttagcc tggtagaact tggactcgcc aatgtggaag gattatctgt tctccgttca 2580 tttcgattgc tgcgagtttt caagttggca aaatcttggc caacgttaaa tatgctaata 2640 aagatcatcg gcaattccgt gggggctctg ggaaatttaa ccctcgtctt ggccatcatc 2700 gtcttcattt ttgccgtggt cggcatgcag ctctttggta aaagctacaa agattgtgtc 2760 tgcaagatcg ccagtgattg tcaactccca cgctggcaca tgaatgactt cttccactcc 2820 ttcctgattg tgttccgcgt gctgtgtggg gagtggatag agaccatgtg ggactgtatg 2880 gaggttgctg gtcaagccat gtgccttact gtcttcatga tggtcatggt gattggaaac 2940 ctagtggtcc tgaatctctt tctggccttg cttmtgagct catttagtgc agacaacctt 3000 gcagccactg atgatgataa tgaaatgaat aatctccaaa ttgctgtgga taggatgcac 3060 aaaggagtag cttatgtgaa aagaaaaata tatgaattta ttcaacagtc cttcattagg 3120 aaacaaaaga ttttagatga aattaaacca cttgatgatc taaacaacaa gaaagacagt 3180 tgtatgtcca atcatacarc agaaattggg aaagatcttg actatcttaa agatgtaaat 3240 ggaactacaa gtggtatagg aactggcagc agtgttgaaa aatacattat tgatgaaagt 3300 gattacatgt cattcataaa caaccccagt cttactgtga ctgtaccaat tgctgtagga 3360 gaatctgact ttgaaaattt aaacacggaa gactttagta gtgaatcgga tctggaagaa 3420 agcaaagaga aactgaatga aagcagtagc tcatcagaag gtagcactgt ggacatcggc 3480 gcacctgtag aagaacagcc cgtagtggaa cctgaagaaa ctcttgaacc agaagcttgt 3540 ttcactgaag gctgtgtaca aagattcaag tgttgtcaaa tcaatgtgga agaaggcaga 3600 ggaaaacaat ggtggaacct gagaaggacg tgtttccgaa tagttgaaca taactggttt 3660 gagaccttca ttgttttcat gattctcctt agtagtggtg ctctggcatt tgaagatata 3720 tatattgatc agcgaaagac gattaagacg atgttggaat atgctgacaa ggttttcact 3780 tacattttca ttctggaaat gcttctaaaa tgggtggcat atggctatca aacatatttc 3840 accaatgcct ggtgttggct ggacttctta attgttgatg tttcattggt cagtttaaca 3900 gcaaatgcct tgggttactc agaacttgga gccatcaaat ctctcaggac actaagagct 3960 ctgagacctc taagagcctt atctcgattt gaagggatga gggtggttgt gaatgccctt 4020 ttaggagcaa ttccatccat catgaatgtg cttctggttt gtcttatatt ctggctaatt 4080 ttcagcatca tgggcgtaaa tttgtttgct ggcaaattct accactgtat taacaccaca 4140 actggtgaca ggtttgacat cgaagacgtg aataatcata ctgattgcct aaaactaata 4200 gaaagaaatg agactgctcg atggaaaaat gtgaaagtaa actttgataa tgtaggattt 4260 gggtatctct ctttgcttca agttgccaca ttcaaaggat ggatggatat aatgtatgca 4320 gcagttgatt ccagaaatgt ggaactccag cctaagtatg aagaaagtct gtacatgtat 4380 ctttactttg ttattttcat catctttggg tccttcttca ccttgaacct gtttattggt 4440 gtcatcatag ataatttcaa ccagcagaaa aagaagtttg gaggtcaaga catctttatg 4500 acagaagaac agaagaaata ctataatgca atgaaaaaat taggatcgaa aaaaccgcaa 4560 aagcctatac ctcgaccagg aaacaaattt caaggaatgg tctttgactt cgtaaccaga 4620 caagtttttg acataagcat catgattctc atctgtctta acatggtcac aatgatggtg 4680 gaaacagatg accagagtga atatgtgact accattttgt cacgcatcaa tctggtgttc 4740 attgtgctat ttactggaga gtgtgtactg aaactcatct ctctacgcca ttattatttt 4800 accattggat ggaatatttt tgattttgtg gttgtcattc tctccattgt aggtatgttt 4860 cttgccgagc tgatagaaaa gtatttcgtg tcccctaccc tgttccgagt gatccgtctt 4920 gctaggattg gccgaatcct acgtctgatc aaaggagcaa aggggatccg cacgctgctc 4980 tttgctttga tgatgtccct tcctgcgttg tttaacatcg gcctcctact cttcctagtc 5040 atgttcatct acgccatctt tgggatgtcc aactttgcct atgttaagag ggaagttggg 5100 atcgatgaca tgttcaactt tgagaccttt ggcaacagca tgatctgcct attccaaatt 5160 acaacctctg ctggctggga tggattgcta gcacccattc tcaacagtaa gccacccgac 5220 tgtgacccta ataaagttaa ccctggaagc tcagttaagg gagactgtgg gaacccatct 5280 gttggaattt tcttttttgt cagttacatc atcatatcct tcctggttgt ggtgaacatg 5340 tacatcgcgg tcatcctgga gaacttcagt gttgctactg aagaaagtgc agagcctctg 5400 agtgaggatg actttgagat gttctatgag gtttgggaga agtttgatcc cgatgcaact 5460 cagttcatgg aatttgaaaa attatctcag tttgcagctg cgcttgaacc gcctctcaat 5520 ctgccacaac caaacaaact ccagctcatt gccatggatt tgcccatggt gagtggtgac 5580 cggatccact gtcttgatat cttatttgct tttacaaagc gggttctagg agagagtgga 5640 gagatggatg ctctacgaat acagatggaa gagcgattca tggcttccaa tccttccaag 5700 gtctcctatc agccaatcac tactacttta aaacgaaaac aagaggaagt atctgctgtc 5760 attattcagc gtgcttacag acgccacctt ttaaagcgaa ctgtaaaaca agcttccttt 5820 acgtacaata aaaacaaaat caaaggtggg gctaatcttc ttataaaaga agacatgata 5880 attgacagaa taaatgaaaa ctctattaca gaaaaaaact ga 5922 14 1973 PRT homo sapiens VARIANT (1)...(1973) Xaa = Any Amino Acid 14 Met Glu Gln Thr Val Leu Val Pro Pro Gly Pro Asp Ser Phe Asn Phe 1 5 10 15 Phe Thr Arg Glu Ser Leu Ala Ala Ile Glu Arg Arg Ile Ala Glu Glu 20 25 30 Lys Ala Lys Asn Pro Lys Pro Asp Lys Lys Asp Asp Asp Glu Asn Gly 35 40 45 Pro Lys Pro Asn Ser Asp Leu Glu Ala Gly Lys Asn Leu Pro Phe Ile 50 55 60 Tyr Gly Asp Ile Pro Pro Glu Met Val Ser Glu Pro Leu Glu Asp Leu 65 70 75 80 Asp Pro Tyr Tyr Ile Asn Lys Lys Thr Phe Ile Val Leu Asn Lys Gly 85 90 95 Lys Ala Ile Phe Arg Phe Ser Ala Thr Ser Ala Leu Tyr Ile Leu Thr 100 105 110 Pro Phe Asn Pro Leu Arg Lys Ile Ala Ile Lys Ile Leu Val His Ser 115 120 125 Leu Phe Ser Met Leu Ile Met Cys Thr Ile Leu Thr Asn Cys Val Phe 130 135 140 Met Thr Met Ser Asn Pro Pro Asp Trp Thr Lys Asn Val Glu Tyr Thr 145 150 155 160 Phe Thr Gly Ile Tyr Thr Phe Glu Ser Leu Ile Lys Ile Ile Ala Arg 165 170 175 Gly Phe Cys Leu Glu Asp Phe Thr Phe Leu Arg Asp Pro Trp Asn Trp 180 185 190 Leu Asp Phe Thr Val Ile Thr Phe Ala Tyr Val Thr Glu Phe Val Asp 195 200 205 Leu Gly Asn Val Ser Ala Leu Arg Thr Phe Arg Val Leu Arg Ala Leu 210 215 220 Lys Thr Ile Ser Val Ile Pro Gly Leu Lys Thr Ile Val Gly Ala Leu 225 230 235 240 Ile Gln Ser Val Lys Lys Leu Ser Asp Val Met Ile Leu Thr Val Phe 245 250 255 Cys Leu Ser Val Phe Ala Leu Ile Gly Leu Gln Leu Phe Met Gly Asn 260 265 270 Leu Arg Asn Lys Cys Ile Gln Trp Pro Pro Thr Asn Ala Ser Leu Glu 275 280 285 Glu His Ser Ile Glu Lys Asn Ile Thr Val Asn Tyr Asn Gly Thr Leu 290 295 300 Ile Asn Glu Thr Val Phe Glu Phe Asp Trp Lys Ser Tyr Ile Gln Asp 305 310 315 320 Ser Arg Tyr His Tyr Phe Leu Glu Gly Phe Leu Asp Ala Leu Leu Cys 325 330 335 Gly Asn Ser Ser Asp Ala Gly Gln Cys Pro Glu Gly Tyr Met Cys Val 340 345 350 Lys Ala Gly Arg Asn Pro Asn Tyr Gly Tyr Thr Ser Phe Asp Thr Phe 355 360 365 Ser Trp Ala Phe Leu Ser Leu Phe Arg Leu Met Thr Gln Asp Phe Trp 370 375 380 Glu Asn Leu Tyr Gln Leu Thr Leu Arg Ala Ala Gly Lys Thr Tyr Met 385 390 395 400 Ile Phe Phe Val Leu Val Ile Phe Leu Gly Ser Phe Tyr Leu Ile Asn 405 410 415 Leu Ile Leu Ala Val Val Ala Met Ala Tyr Glu Glu Gln Asn Gln Ala 420 425 430 Thr Leu Glu Glu Ala Glu Gln Lys Glu Ala Glu Phe Gln Gln Met Ile 435 440 445 Glu Gln Leu Lys Lys Gln Gln Glu Ala Ala Gln Gln Ala Ala Thr Ala 450 455 460 Thr Ala Ser Glu His Ser Arg Glu Pro Ser Ala Ala Gly Arg Leu Ser 465 470 475 480 Asp Ser Ser Ser Glu Ala Ser Lys Leu Ser Ser Lys Ser Ala Lys Glu 485 490 495 Arg Arg Asn Arg Arg Lys Lys Arg Lys Gln Lys Glu Gln Ser Gly Gly 500 505 510 Glu Glu Lys Asp Glu Asp Glu Phe Gln Lys Ser Glu Ser Glu Asp Ser 515 520 525 Ile Arg Arg Lys Gly Phe Arg Phe Ser Ile Glu Gly Asn Arg Leu Thr 530 535 540 Tyr Glu Lys Arg Tyr Ser Ser Pro His Gln Ser Leu Leu Ser Ile Arg 545 550 555 560 Gly Ser Leu Phe Ser Pro Arg Arg Asn Ser Arg Thr Ser Leu Phe Ser 565 570 575 Phe Arg Gly Arg Ala Lys Asp Val Gly Ser Glu Asn Asp Phe Ala Asp 580 585 590 Asp Glu His Ser Thr Phe Glu Asp Asn Glu Ser Arg Arg Asp Ser Leu 595 600 605 Phe Val Pro Arg Arg His Gly Glu Arg Arg Asn Ser Asn Leu Ser Gln 610 615 620 Thr Ser Arg Ser Ser Arg Met Leu Ala Val Phe Pro Ala Asn Gly Lys 625 630 635 640 Met His Ser Thr Val Asp Cys Asn Gly Val Val Ser Leu Val Gly Gly 645 650 655 Pro Ser Val Pro Thr Ser Pro Val Gly Gln Leu Leu Pro Glu Val Ile 660 665 670 Ile Asp Lys Pro Ala Thr Asp Asp Asn Gly Thr Thr Thr Glu Thr Glu 675 680 685 Met Arg Lys Arg Arg Ser Ser Ser Phe His Val Ser Met Asp Phe Leu 690 695 700 Glu Asp Pro Ser Gln Arg Gln Arg Ala Met Ser Ile Ala Ser Ile Leu 705 710 715 720 Thr Asn Thr Val Glu Glu Leu Glu Glu Ser Arg Gln Lys Cys Pro Pro 725 730 735 Cys Trp Tyr Lys Phe Ser Asn Ile Phe Leu Ile Trp Asp Cys Ser Pro 740 745 750 Tyr Trp Leu Lys Val Lys His Val Val Asn Leu Val Val Met Asp Pro 755 760 765 Phe Val Asp Leu Ala Ile Thr Ile Cys Ile Val Leu Asn Thr Leu Phe 770 775 780 Met Ala Met Glu His Tyr Pro Met Thr Asp His Phe Asn Asn Val Leu 785 790 795 800 Thr Val Gly Asn Leu Val Phe Thr Gly Ile Phe Thr Ala Glu Met Phe 805 810 815 Leu Lys Ile Ile Ala Met Asp Pro Tyr Tyr Tyr Phe Gln Glu Gly Trp 820 825 830 Asn Ile Phe Asp Gly Phe Ile Val Thr Leu Ser Leu Val Glu Leu Gly 835 840 845 Leu Ala Asn Val Glu Gly Leu Ser Val Leu Arg Ser Phe Arg Leu Leu 850 855 860 Arg Val Phe Lys Leu Ala Lys Ser Trp Pro Thr Leu Asn Met Leu Ile 865 870 875 880 Lys Ile Ile Gly Asn Ser Val Gly Ala Leu Gly Asn Leu Thr Leu Val 885 890 895 Leu Ala Ile Ile Val Phe Ile Phe Ala Val Val Gly Met Gln Leu Phe 900 905 910 Gly Lys Ser Tyr Lys Asp Cys Val Cys Lys Ile Ala Ser Asp Cys Gln 915 920 925 Leu Pro Arg Trp His Met Asn Asp Phe Phe His Ser Phe Leu Ile Val 930 935 940 Phe Arg Val Leu Cys Gly Glu Trp Ile Glu Thr Met Trp Asp Cys Met 945 950 955 960 Glu Val Ala Gly Gln Ala Met Cys Leu Thr Val Phe Met Met Val Met 965 970 975 Val Ile Gly Asn Leu Val Val Leu Asn Leu Phe Leu Ala Leu Leu Xaa 980 985 990 Ser Ser Phe Ser Ala Asp Asn Leu Ala Ala Thr Asp Asp Asp Asn Glu 995 1000 1005 Met Asn Asn Leu Gln Ile Ala Val Asp Arg Met His Lys Gly Val Ala 1010 1015 1020 Tyr Val Lys Arg Lys Ile Tyr Glu Phe Ile Gln Gln Ser Phe Ile Arg 1025 1030 1035 1040 Lys Gln Lys Ile Leu Asp Glu Ile Lys Pro Leu Asp Asp Leu Asn Asn 1045 1050 1055 Lys Lys Asp Ser Cys Met Ser Asn His Thr Xaa Glu Ile Gly Lys Asp 1060 1065 1070 Leu Asp Tyr Leu Lys Asp Val Asn Gly Thr Thr Ser Gly Ile Gly Thr 1075 1080 1085 Gly Ser Ser Val Glu Lys Tyr Ile Ile Asp Glu Ser Asp Tyr Met Ser 1090 1095 1100 Phe Ile Asn Asn Pro Ser Leu Thr Val Thr Val Pro Ile Ala Val Gly 1105 1110 1115 1120 Glu Ser Asp Phe Glu Asn Leu Asn Thr Glu Asp Phe Ser Ser Glu Ser 1125 1130 1135 Asp Leu Glu Glu Ser Lys Glu Lys Leu Asn Glu Ser Ser Ser Ser Ser 1140 1145 1150 Glu Gly Ser Thr Val Asp Ile Gly Ala Pro Val Glu Glu Gln Pro Val 1155 1160 1165 Val Glu Pro Glu Glu Thr Leu Glu Pro Glu Ala Cys Phe Thr Glu Gly 1170 1175 1180 Cys Val Gln Arg Phe Lys Cys Cys Gln Ile Asn Val Glu Glu Gly Arg 1185 1190 1195 1200 Gly Lys Gln Trp Trp Asn Leu Arg Arg Thr Cys Phe Arg Ile Val Glu 1205 1210 1215 His Asn Trp Phe Glu Thr Phe Ile Val Phe Met Ile Leu Leu Ser Ser 1220 1225 1230 Gly Ala Leu Ala Phe Glu Asp Ile Tyr Ile Asp Gln Arg Lys Thr Ile 1235 1240 1245 Lys Thr Met Leu Glu Tyr Ala Asp Lys Val Phe Thr Tyr Ile Phe Ile 1250 1255 1260 Leu Glu Met Leu Leu Lys Trp Val Ala Tyr Gly Tyr Gln Thr Tyr Phe 1265 1270 1275 1280 Thr Asn Ala Trp Cys Trp Leu Asp Phe Leu Ile Val Asp Val Ser Leu 1285 1290 1295 Val Ser Leu Thr Ala Asn Ala Leu Gly Tyr Ser Glu Leu Gly Ala Ile 1300 1305 1310 Lys Ser Leu Arg Thr Leu Arg Ala Leu Arg Pro Leu Arg Ala Leu Ser 1315 1320 1325 Arg Phe Glu Gly Met Arg Val Val Val Asn Ala Leu Leu Gly Ala Ile 1330 1335 1340 Pro Ser Ile Met Asn Val Leu Leu Val Cys Leu Ile Phe Trp Leu Ile 1345 1350 1355 1360 Phe Ser Ile Met Gly Val Asn Leu Phe Ala Gly Lys Phe Tyr His Cys 1365 1370 1375 Ile Asn Thr Thr Thr Gly Asp Arg Phe Asp Ile Glu Asp Val Asn Asn 1380 1385 1390 His Thr Asp Cys Leu Lys Leu Ile Glu Arg Asn Glu Thr Ala Arg Trp 1395 1400 1405 Lys Asn Val Lys Val Asn Phe Asp Asn Val Gly Phe Gly Tyr Leu Ser 1410 1415 1420 Leu Leu Gln Val Ala Thr Phe Lys Gly Trp Met Asp Ile Met Tyr Ala 1425 1430 1435 1440 Ala Val Asp Ser Arg Asn Val Glu Leu Gln Pro Lys Tyr Glu Glu Ser 1445 1450 1455 Leu Tyr Met Tyr Leu Tyr Phe Val Ile Phe Ile Ile Phe Gly Ser Phe 1460 1465 1470 Phe Thr Leu Asn Leu Phe Ile Gly Val Ile Ile Asp Asn Phe Asn Gln 1475 1480 1485 Gln Lys Lys Lys Phe Gly Gly Gln Asp Ile Phe Met Thr Glu Glu Gln 1490 1495 1500 Lys Lys Tyr Tyr Asn Ala Met Lys Lys Leu Gly Ser Lys Lys Pro Gln 1505 1510 1515 1520 Lys Pro Ile Pro Arg Pro Gly Asn Lys Phe Gln Gly Met Val Phe Asp 1525 1530 1535 Phe Val Thr Arg Gln Val Phe Asp Ile Ser Ile Met Ile Leu Ile Cys 1540 1545 1550 Leu Asn Met Val Thr Met Met Val Glu Thr Asp Asp Gln Ser Glu Tyr 1555 1560 1565 Val Thr Thr Ile Leu Ser Arg Ile Asn Leu Val Phe Ile Val Leu Phe 1570 1575 1580 Thr Gly Glu Cys Val Leu Lys Leu Ile Ser Leu Arg His Tyr Tyr Phe 1585 1590 1595 1600 Thr Ile Gly Trp Asn Ile Phe Asp Phe Val Val Val Ile Leu Ser Ile 1605 1610 1615 Val Gly Met Phe Leu Ala Glu Leu Ile Glu Lys Tyr Phe Val Ser Pro 1620 1625 1630 Thr Leu Phe Arg Val Ile Arg Leu Ala Arg Ile Gly Arg Ile Leu Arg 1635 1640 1645 Leu Ile Lys Gly Ala Lys Gly Ile Arg Thr Leu Leu Phe Ala Leu Met 1650 1655 1660 Met Ser Leu Pro Ala Leu Phe Asn Ile Gly Leu Leu Leu Phe Leu Val 1665 1670 1675 1680 Met Phe Ile Tyr Ala Ile Phe Gly Met Ser Asn Phe Ala Tyr Val Lys 1685 1690 1695 Arg Glu Val Gly Ile Asp Asp Met Phe Asn Phe Glu Thr Phe Gly Asn 1700 1705 1710 Ser Met Ile Cys Leu Phe Gln Ile Thr Thr Ser Ala Gly Trp Asp Gly 1715 1720 1725 Leu Leu Ala Pro Ile Leu Asn Ser Lys Pro Pro Asp Cys Asp Pro Asn 1730 1735 1740 Lys Val Asn Pro Gly Ser Ser Val Lys Gly Asp Cys Gly Asn Pro Ser 1745 1750 1755 1760 Val Gly Ile Phe Phe Phe Val Ser Tyr Ile Ile Ile Ser Phe Leu Val 1765 1770 1775 Val Val Asn Met Tyr Ile Ala Val Ile Leu Glu Asn Phe Ser Val Ala 1780 1785 1790 Thr Glu Glu Ser Ala Glu Pro Leu Ser Glu Asp Asp Phe Glu Met Phe 1795 1800 1805 Tyr Glu Val Trp Glu Lys Phe Asp Pro Asp Ala Thr Gln Phe Met Glu 1810 1815 1820 Phe Glu Lys Leu Ser Gln Phe Ala Ala Ala Leu Glu Pro Pro Leu Asn 1825 1830 1835 1840 Leu Pro Gln Pro Asn Lys Leu Gln Leu Ile Ala Met Asp Leu Pro Met 1845 1850 1855 Val Ser Gly Asp Arg Ile His Cys Leu Asp Ile Leu Phe Ala Phe Thr 1860 1865 1870 Lys Arg Val Leu Gly Glu Ser Gly Glu Met Asp Ala Leu Arg Ile Gln 1875 1880 1885 Met Glu Glu Arg Phe Met Ala Ser Asn Pro Ser Lys Val Ser Tyr Gln 1890 1895 1900 Pro Ile Thr Thr Thr Leu Lys Arg Lys Gln Glu Glu Val Ser Ala Val 1905 1910 1915 1920 Ile Ile Gln Arg Ala Tyr Arg Arg His Leu Leu Lys Arg Thr Val Lys 1925 1930 1935 Gln Ala Ser Phe Thr Tyr Asn Lys Asn Lys Ile Lys Gly Gly Ala Asn 1940 1945 1950 Leu Leu Ile Lys Glu Asp Met Ile Ile Asp Arg Ile Asn Glu Asn Ser 1955 1960 1965 Ile Thr Glu Lys Asn 1970 15 4362 DNA homo sapiens 15 atggagcaaa cagtgcttgt accaccagga cctgacagct tcaacttctt caccagagaa 60 tctcttgcgg ctattgaaag acgcattgca gaagaaaagg caaagaatcc caaaccagac 120 aaaaaagatg acgacgaaaa tggcccaaag ccaaatagtg acttggaagc tggaaagaac 180 cttccattta tttatggaga cattcctcca gagatggtgt cagagcccct ggaggacctg 240 gacccctact atatcaataa gaaaactttt atagtattga ataaagggaa ggccatcttc 300 cggttcagtg ccacctctgc cctgtacatt ttaactccct tcaatcctct taggaaaata 360 gctattaaga ttttggtaca ttcattattc agcatgctaa ttatgtgcac tattttgaca 420 aactgtgtgt ttatgacaat gagtaaccct cctgattgga caaagaatgt agaatacacc 480 ttcacaggaa tatatacttt tgaatcactt ataaaaatta ttgcaagggg attctgttta 540 gaagatttta ctttccttcg ggatccatgg aactggctcg atttcactgt cattacattt 600 gcgtacgtca cagagtttgt ggacctgggc aatgtctcgg cattgagaac attcagagtt 660 ctccgagcat tgaagacgat ttcagtcatt ccaggcctga aaaccattgt gggagccctg 720 atccagtctg tgaagaagct ctcagatgta atgatcctga ctgtgttctg tctgagcgta 780 tttgctctaa ttgggctgca gctgttcatg ggcaacctga ggaataaatg tatacaatgg 840 cctcccacca atgcttcctt ggaggaacat agtatagaaa agaatataac tgtgaattat 900 aatggtacac ttataaatga aactgtcttt gagtttgact ggaagtcata tattcaagat 960 tcaagatatc attatttcct ggagggtttt ttagatgcac tactatgtgg aaatagctct 1020 gatgcaggcc aatgtccaga gggatatatg tgtgtgaaag ctggtagaaa tcccaattat 1080 ggctacacaa gctttgatac cttcagttgg gcttttttgt ccttgtttcg actaatgact 1140 caggacttct gggaaaatct ttatcaactg acattacgtg ctgctgggaa aacgtacatg 1200 atattttttg tgttggtcat tttcttgggc tcattctacc taataaattt gatcctggct 1260 gtggtggcca tggcctacga ggaacagaat caggccacct tggaagaagc agaacagaaa 1320 gaggccgaat ttcagcagat gattgaacag cttaaaaagc aacaggaggc agctcagcag 1380 gcagcaacgg caactgcctc agaacattcc agagagccca gtgcagcagg caggctctca 1440 gacagctcat ctgaagcctc taagttgagt tccaagagtg ctaaggaaag aagaaatcgg 1500 aggaagaaaa gaaaacagaa agagcagtct ggtggggaag agaaagatga ggatgaattc 1560 caaaaatctg aatctgagga cagcatcagg aggaaaggtt ttcgcttctc cattgaaggg 1620 aaccgattga catatgaaaa gaggtactcc tccccacacc agtctttgtt gagcatccgt 1680 ggctccctat tttcaccaag gcgaaatagc agaacaagcc ttttcagctt tagagggcga 1740 gcaaaggatg tgggatctga gaacgacttc gcagatgatg agcacagcac ctttgaggat 1800 aacgagagcc gtagagattc cttgtttgtg ccccgacgac acggagagag acgcaacagc 1860 aacctgagtc agaccagtag gtcatcccgg atgctggcag tgtttccagc gaatgggaag 1920 atgcacagca ctgtggattg caatggtgtg gtttccttgg ttggtggacc ttcagttcct 1980 acatcgcctg ttggacagct tctgccagag gtgataatag ataagccagc tactgatgac 2040 aatggaacaa ccactgaaac tgaaatgaga aagagaaggt caagttcttt ccacgtttcc 2100 atggactttc tagaagatcc ttcccaaagg caacgagcaa tgagtatagc cagcattcta 2160 acaaatacag tagaagaact tgaagaatcc aggcagaaat gcccaccctg ttggtataaa 2220 ttttccaaca tattcttaat ctgggactgt tctccatatt ggttaaaagt gaaacatgtt 2280 gtcaacctgg tygtgatgga cccatttgtt gacctggcca tcaccatctg tattgtctta 2340 aatactcttt tcatggccat ggagcactat ccaatgacgg accatttcaa taatgtgctt 2400 acagtaggaa acttggtttt cactgggatc tttacagcag aaatgtttct gaaaattatt 2460 gccatggatc cttactatta tttccaagaa ggctggaata tctttgacgg ttttattgtg 2520 acgcttagcc tggtagaact tggactcgcc aatgtggaag gattatctgt tctccgttca 2580 tttcgattgc tgcgagtttt caagttggca aaatcttggc caacgttaaa tatgctaata 2640 aagatcatcg gcaattccgt gggggctctg ggaaatttaa ccctcgtctt ggccatcatc 2700 gtcttcattt ttgccgtggt cggcatgcag ctctttggta aaagctacaa agattgtgtc 2760 tgcaagatcg ccagtgattg tcaactccca cgctggcaca tgaatgactt cttccactcc 2820 ttcctgattg tgttccgcgt gctgtgtggg gagtggatag agaccatgtg ggactgtatg 2880 gaggttgctg gtcaagccat gtgccttact gtcttcatga tggtcatggt gattggaaac 2940 ctagtggtcc tgaatctctt tctggccttg cttmtgagct catttagtgc agacaacctt 3000 gcagccactg atgatgataa tgaaatgaat aatctccaaa ttgctgtgga taggatgcac 3060 aaaggagtag cttatgtgaa aagaaaaata tatgaattta ttcaacagtc cttcattagg 3120 aaacaaaaga ttttagatga aattaaacca cttgatgatc taaacaacaa gaaagacagt 3180 tgtatgtcca atcatacarc agaaattggg aaagatcttg actatcttaa agatgtaaat 3240 ggaactacaa gtggtatagg aactggcagc agtgttgaaa aatacattat tgatgaaagt 3300 gattacatgt cattcataaa caaccccagt cttactgtga ctgtaccaat tgctgtagga 3360 gaatctgact ttgaaaattt aaacacggaa gactttagta gtgaatcgga tctggaagaa 3420 agcaaagaga aactgaatga aagcagtagc tcatcagaag gtagcactgt ggacatcggc 3480 gcacctgtag aagaacagcc cgtagtggaa cctgaagaaa ctcttgaacc agaagcttgt 3540 ttcactgaag gctgtgtaca aagattcaag tgttgtcaaa tcaatgtgga agaaggcaga 3600 ggaaaacaat ggtggaacct gagaaggacg tgtttccgaa tagttgaaca taactggttt 3660 gagaccttca ttgttttcat gattctcctt agtagtggtg ctctggcatt tgaagatata 3720 tatattgatc agcgaaagac gattaagacg atgttggaat atgctgacaa ggttttcact 3780 tacattttca ttctggaaat gcttctaaaa tgggtggcat atggctatca aacatatttc 3840 accaatgcct ggtgttggct ggacttctta attgttgatg tttcattggt cagtttaaca 3900 gcaaatgcct tgggttactc agaacttgga gccatcaaat ctctcaggac actaagagct 3960 ctgagacctc taagagcctt atctcgattt gaagggatga gggtggttgt gaatgccctt 4020 ttaggagcaa ttccatccat catgaatgtg cttctggttt gtcttatatt ctggctaatt 4080 ttcagcatca tgggcgtaaa tttgtttgct ggcaaattct accactgtat taacaccaca 4140 actggtgaca ggtttgacat cgaagacgtg aataatcata ctgattgcct aaaactaata 4200 gaaagaaatg agactgctcg atggaaaaat gtgaaagtaa actttgataa tgtaggattt 4260 gggtatctct ctttgcttca agttgccaca ttcaaaggat ggatggatat aatgtatgca 4320 gcagttgatt ccagaaatcc tctttcaggc tccaagacct aa 4362 16 1453 PRT homo sapiens VARIANT (1)...(1453) Xaa = Any Amino Acid 16 Met Glu Gln Thr Val Leu Val Pro Pro Gly Pro Asp Ser Phe Asn Phe 1 5 10 15 Phe Thr Arg Glu Ser Leu Ala Ala Ile Glu Arg Arg Ile Ala Glu Glu 20 25 30 Lys Ala Lys Asn Pro Lys Pro Asp Lys Lys Asp Asp Asp Glu Asn Gly 35 40 45 Pro Lys Pro Asn Ser Asp Leu Glu Ala Gly Lys Asn Leu Pro Phe Ile 50 55 60 Tyr Gly Asp Ile Pro Pro Glu Met Val Ser Glu Pro Leu Glu Asp Leu 65 70 75 80 Asp Pro Tyr Tyr Ile Asn Lys Lys Thr Phe Ile Val Leu Asn Lys Gly 85 90 95 Lys Ala Ile Phe Arg Phe Ser Ala Thr Ser Ala Leu Tyr Ile Leu Thr 100 105 110 Pro Phe Asn Pro Leu Arg Lys Ile Ala Ile Lys Ile Leu Val His Ser 115 120 125 Leu Phe Ser Met Leu Ile Met Cys Thr Ile Leu Thr Asn Cys Val Phe 130 135 140 Met Thr Met Ser Asn Pro Pro Asp Trp Thr Lys Asn Val Glu Tyr Thr 145 150 155 160 Phe Thr Gly Ile Tyr Thr Phe Glu Ser Leu Ile Lys Ile Ile Ala Arg 165 170 175 Gly Phe Cys Leu Glu Asp Phe Thr Phe Leu Arg Asp Pro Trp Asn Trp 180 185 190 Leu Asp Phe Thr Val Ile Thr Phe Ala Tyr Val Thr Glu Phe Val Asp 195 200 205 Leu Gly Asn Val Ser Ala Leu Arg Thr Phe Arg Val Leu Arg Ala Leu 210 215 220 Lys Thr Ile Ser Val Ile Pro Gly Leu Lys Thr Ile Val Gly Ala Leu 225 230 235 240 Ile Gln Ser Val Lys Lys Leu Ser Asp Val Met Ile Leu Thr Val Phe 245 250 255 Cys Leu Ser Val Phe Ala Leu Ile Gly Leu Gln Leu Phe Met Gly Asn 260 265 270 Leu Arg Asn Lys Cys Ile Gln Trp Pro Pro Thr Asn Ala Ser Leu Glu 275 280 285 Glu His Ser Ile Glu Lys Asn Ile Thr Val Asn Tyr Asn Gly Thr Leu 290 295 300 Ile Asn Glu Thr Val Phe Glu Phe Asp Trp Lys Ser Tyr Ile Gln Asp 305 310 315 320 Ser Arg Tyr His Tyr Phe Leu Glu Gly Phe Leu Asp Ala Leu Leu Cys 325 330 335 Gly Asn Ser Ser Asp Ala Gly Gln Cys Pro Glu Gly Tyr Met Cys Val 340 345 350 Lys Ala Gly Arg Asn Pro Asn Tyr Gly Tyr Thr Ser Phe Asp Thr Phe 355 360 365 Ser Trp Ala Phe Leu Ser Leu Phe Arg Leu Met Thr Gln Asp Phe Trp 370 375 380 Glu Asn Leu Tyr Gln Leu Thr Leu Arg Ala Ala Gly Lys Thr Tyr Met 385 390 395 400 Ile Phe Phe Val Leu Val Ile Phe Leu Gly Ser Phe Tyr Leu Ile Asn 405 410 415 Leu Ile Leu Ala Val Val Ala Met Ala Tyr Glu Glu Gln Asn Gln Ala 420 425 430 Thr Leu Glu Glu Ala Glu Gln Lys Glu Ala Glu Phe Gln Gln Met Ile 435 440 445 Glu Gln Leu Lys Lys Gln Gln Glu Ala Ala Gln Gln Ala Ala Thr Ala 450 455 460 Thr Ala Ser Glu His Ser Arg Glu Pro Ser Ala Ala Gly Arg Leu Ser 465 470 475 480 Asp Ser Ser Ser Glu Ala Ser Lys Leu Ser Ser Lys Ser Ala Lys Glu 485 490 495 Arg Arg Asn Arg Arg Lys Lys Arg Lys Gln Lys Glu Gln Ser Gly Gly 500 505 510 Glu Glu Lys Asp Glu Asp Glu Phe Gln Lys Ser Glu Ser Glu Asp Ser 515 520 525 Ile Arg Arg Lys Gly Phe Arg Phe Ser Ile Glu Gly Asn Arg Leu Thr 530 535 540 Tyr Glu Lys Arg Tyr Ser Ser Pro His Gln Ser Leu Leu Ser Ile Arg 545 550 555 560 Gly Ser Leu Phe Ser Pro Arg Arg Asn Ser Arg Thr Ser Leu Phe Ser 565 570 575 Phe Arg Gly Arg Ala Lys Asp Val Gly Ser Glu Asn Asp Phe Ala Asp 580 585 590 Asp Glu His Ser Thr Phe Glu Asp Asn Glu Ser Arg Arg Asp Ser Leu 595 600 605 Phe Val Pro Arg Arg His Gly Glu Arg Arg Asn Ser Asn Leu Ser Gln 610 615 620 Thr Ser Arg Ser Ser Arg Met Leu Ala Val Phe Pro Ala Asn Gly Lys 625 630 635 640 Met His Ser Thr Val Asp Cys Asn Gly Val Val Ser Leu Val Gly Gly 645 650 655 Pro Ser Val Pro Thr Ser Pro Val Gly Gln Leu Leu Pro Glu Val Ile 660 665 670 Ile Asp Lys Pro Ala Thr Asp Asp Asn Gly Thr Thr Thr Glu Thr Glu 675 680 685 Met Arg Lys Arg Arg Ser Ser Ser Phe His Val Ser Met Asp Phe Leu 690 695 700 Glu Asp Pro Ser Gln Arg Gln Arg Ala Met Ser Ile Ala Ser Ile Leu 705 710 715 720 Thr Asn Thr Val Glu Glu Leu Glu Glu Ser Arg Gln Lys Cys Pro Pro 725 730 735 Cys Trp Tyr Lys Phe Ser Asn Ile Phe Leu Ile Trp Asp Cys Ser Pro 740 745 750 Tyr Trp Leu Lys Val Lys His Val Val Asn Leu Val Val Met Asp Pro 755 760 765 Phe Val Asp Leu Ala Ile Thr Ile Cys Ile Val Leu Asn Thr Leu Phe 770 775 780 Met Ala Met Glu His Tyr Pro Met Thr Asp His Phe Asn Asn Val Leu 785 790 795 800 Thr Val Gly Asn Leu Val Phe Thr Gly Ile Phe Thr Ala Glu Met Phe 805 810 815 Leu Lys Ile Ile Ala Met Asp Pro Tyr Tyr Tyr Phe Gln Glu Gly Trp 820 825 830 Asn Ile Phe Asp Gly Phe Ile Val Thr Leu Ser Leu Val Glu Leu Gly 835 840 845 Leu Ala Asn Val Glu Gly Leu Ser Val Leu Arg Ser Phe Arg Leu Leu 850 855 860 Arg Val Phe Lys Leu Ala Lys Ser Trp Pro Thr Leu Asn Met Leu Ile 865 870 875 880 Lys Ile Ile Gly Asn Ser Val Gly Ala Leu Gly Asn Leu Thr Leu Val 885 890 895 Leu Ala Ile Ile Val Phe Ile Phe Ala Val Val Gly Met Gln Leu Phe 900 905 910 Gly Lys Ser Tyr Lys Asp Cys Val Cys Lys Ile Ala Ser Asp Cys Gln 915 920 925 Leu Pro Arg Trp His Met Asn Asp Phe Phe His Ser Phe Leu Ile Val 930 935 940 Phe Arg Val Leu Cys Gly Glu Trp Ile Glu Thr Met Trp Asp Cys Met 945 950 955 960 Glu Val Ala Gly Gln Ala Met Cys Leu Thr Val Phe Met Met Val Met 965 970 975 Val Ile Gly Asn Leu Val Val Leu Asn Leu Phe Leu Ala Leu Leu Xaa 980 985 990 Ser Ser Phe Ser Ala Asp Asn Leu Ala Ala Thr Asp Asp Asp Asn Glu 995 1000 1005 Met Asn Asn Leu Gln Ile Ala Val Asp Arg Met His Lys Gly Val Ala 1010 1015 1020 Tyr Val Lys Arg Lys Ile Tyr Glu Phe Ile Gln Gln Ser Phe Ile Arg 1025 1030 1035 1040 Lys Gln Lys Ile Leu Asp Glu Ile Lys Pro Leu Asp Asp Leu Asn Asn 1045 1050 1055 Lys Lys Asp Ser Cys Met Ser Asn His Thr Xaa Glu Ile Gly Lys Asp 1060 1065 1070 Leu Asp Tyr Leu Lys Asp Val Asn Gly Thr Thr Ser Gly Ile Gly Thr 1075 1080 1085 Gly Ser Ser Val Glu Lys Tyr Ile Ile Asp Glu Ser Asp Tyr Met Ser 1090 1095 1100 Phe Ile Asn Asn Pro Ser Leu Thr Val Thr Val Pro Ile Ala Val Gly 1105 1110 1115 1120 Glu Ser Asp Phe Glu Asn Leu Asn Thr Glu Asp Phe Ser Ser Glu Ser 1125 1130 1135 Asp Leu Glu Glu Ser Lys Glu Lys Leu Asn Glu Ser Ser Ser Ser Ser 1140 1145 1150 Glu Gly Ser Thr Val Asp Ile Gly Ala Pro Val Glu Glu Gln Pro Val 1155 1160 1165 Val Glu Pro Glu Glu Thr Leu Glu Pro Glu Ala Cys Phe Thr Glu Gly 1170 1175 1180 Cys Val Gln Arg Phe Lys Cys Cys Gln Ile Asn Val Glu Glu Gly Arg 1185 1190 1195 1200 Gly Lys Gln Trp Trp Asn Leu Arg Arg Thr Cys Phe Arg Ile Val Glu 1205 1210 1215 His Asn Trp Phe Glu Thr Phe Ile Val Phe Met Ile Leu Leu Ser Ser 1220 1225 1230 Gly Ala Leu Ala Phe Glu Asp Ile Tyr Ile Asp Gln Arg Lys Thr Ile 1235 1240 1245 Lys Thr Met Leu Glu Tyr Ala Asp Lys Val Phe Thr Tyr Ile Phe Ile 1250 1255 1260 Leu Glu Met Leu Leu Lys Trp Val Ala Tyr Gly Tyr Gln Thr Tyr Phe 1265 1270 1275 1280 Thr Asn Ala Trp Cys Trp Leu Asp Phe Leu Ile Val Asp Val Ser Leu 1285 1290 1295 Val Ser Leu Thr Ala Asn Ala Leu Gly Tyr Ser Glu Leu Gly Ala Ile 1300 1305 1310 Lys Ser Leu Arg Thr Leu Arg Ala Leu Arg Pro Leu Arg Ala Leu Ser 1315 1320 1325 Arg Phe Glu Gly Met Arg Val Val Val Asn Ala Leu Leu Gly Ala Ile 1330 1335 1340 Pro Ser Ile Met Asn Val Leu Leu Val Cys Leu Ile Phe Trp Leu Ile 1345 1350 1355 1360 Phe Ser Ile Met Gly Val Asn Leu Phe Ala Gly Lys Phe Tyr His Cys 1365 1370 1375 Ile Asn Thr Thr Thr Gly Asp Arg Phe Asp Ile Glu Asp Val Asn Asn 1380 1385 1390 His Thr Asp Cys Leu Lys Leu Ile Glu Arg Asn Glu Thr Ala Arg Trp 1395 1400 1405 Lys Asn Val Lys Val Asn Phe Asp Asn Val Gly Phe Gly Tyr Leu Ser 1410 1415 1420 Leu Leu Gln Val Ala Thr Phe Lys Gly Trp Met Asp Ile Met Tyr Ala 1425 1430 1435 1440 Ala Val Asp Ser Arg Asn Pro Leu Ser Gly Ser Lys Thr 1445 1450 17 4179 DNA homo sapiens 17 atggagcaaa cagtgcttgt accaccagga cctgacagct tcaacttctt caccagagaa 60 tctcttgcgg ctattgaaag acgcattgca gaagaaaagg caaagaatcc caaaccagac 120 aaaaaagatg acgacgaaaa tggcccaaag ccaaatagtg acttggaagc tggaaagaac 180 cttccattta tttatggaga cattcctcca gagatggtgt cagagcccct ggaggacctg 240 gacccctact atatcaataa gaaaactttt atagtattga ataaagggaa ggccatcttc 300 cggttcagtg ccacctctgc cctgtacatt ttaactccct tcaatcctct taggaaaata 360 gctattaaga ttttggtaca ttcattattc agcatgctaa ttatgtgcac tattttgaca 420 aactgtgtgt ttatgacaat gagtaaccct cctgattgga caaagaatgt agaatacacc 480 ttcacaggaa tatatacttt tgaatcactt ataaaaatta ttgcaagggg attctgttta 540 gaagatttta ctttccttcg ggatccatgg aactggctcg atttcactgt cattacattt 600 gcgtacgtca cagagtttgt ggacctgggc aatgtctcgg cattgagaac attcagagtt 660 ctccgagcat tgaagacgat ttcagtcatt ccaggcctga aaaccattgt gggagccctg 720 atccagtctg tgaagaagct ctcagatgta atgatcctga ctgtgttctg tctgagcgta 780 tttgctctaa ttgggctgca gctgttcatg ggcaacctga ggaataaatg tatacaatgg 840 cctcccacca atgcttcctt ggaggaacat agtatagaaa agaatataac tgtgaattat 900 aatggtacac ttataaatga aactgtcttt gagtttgact ggaagtcata tattcaagat 960 tcaagatatc attatttcct ggagggtttt ttagatgcac tactatgtgg aaatagctct 1020 gatgcaggcc aatgtccaga gggatatatg tgtgtgaaag ctggtagaaa tcccaattat 1080 ggctacacaa gctttgatac cttcagttgg gcttttttgt ccttgtttcg actaatgact 1140 caggacttct gggaaaatct ttatcaactg acattacgtg ctgctgggaa aacgtacatg 1200 atattttttg tgttggtcat tttcttgggc tcattctacc taataaattt gatcctggct 1260 gtggtggcca tggcctacga ggaacagaat caggccacct tggaagaagc agaacagaaa 1320 gaggccgaat ttcagcagat gattgaacag cttaaaaagc aacaggaggc agctcagcag 1380 gcagcaacgg caactgcctc agaacattcc agagagccca gtgcagcagg caggctctca 1440 gacagctcat ctgaagcctc taagttgagt tccaagagtg ctaaggaaag aagaaatcgg 1500 aggaagaaaa gaaaacagaa agagcagtct ggtggggaag agaaagatga ggatgaattc 1560 caaaaatctg aatctgagga cagcatcagg aggaaaggtt ttcgcttctc cattgaaggg 1620 aaccgattga catatgaaaa gaggtactcc tccccacacc agtctttgtt gagcatccgt 1680 ggctccctat tttcaccaag gcgaaatagc agaacaagcc ttttcagctt tagagggcga 1740 gcaaaggatg tgggatctga gaacgacttc gcagatgatg agcacagcac ctttgaggat 1800 aacgagagcc gtagagattc cttgtttgtg ccccgacgac acggagagag acgcaacagc 1860 aacctgagtc agaccagtag gtcatcccgg atgctggcag tgtttccagc gaatgggaag 1920 atgcacagca ctgtggattg caatggtgtg gtttccttgg ttggtggacc ttcagttcct 1980 acatcgcctg ttggacagct tctgccagag gtgataatag ataagccagc tactgatgac 2040 aatggaacaa ccactgaaac tgaaatgaga aagagaaggt caagttcttt ccacgtttcc 2100 atggactttc tagaagatcc ttcccaaagg caacgagcaa tgagtatagc cagcattcta 2160 acaaatacag tagaagaact tgaagaatcc aggcagaaat gcccaccctg ttggtataaa 2220 ttttccaaca tattcttaat ctgggactgt tctccatatt ggttaaaagt gaaacatgtt 2280 gtcaacctgg tygtgatgga cccatttgtt gacctggcca tcaccatctg tattgtctta 2340 aatactcttt tcatggccat ggagcactat ccaatgacgg accatttcaa taatgtgctt 2400 acagtaggaa acttggtttt cactgggatc tttacagcag aaatgtttct gaaaattatt 2460 gccatggatc cttactatta tttccaagaa ggctggaata tctttgacgg ttttattgtg 2520 acgcttagcc tggtagaact tggactcgcc aatgtggaag gattatctgt tctccgttca 2580 tttcgattgc tgcgagtttt caagttggca aaatcttggc caacgttaaa tatgctaata 2640 aagatcatcg gcaattccgt gggggctctg ggaaatttaa ccctcgtctt ggccatcatc 2700 gtcttcattt ttgccgtggt cggcatgcag ctctttggta aaagctacaa agattgtgtc 2760 tgcaagatcg ccagtgattg tcaactccca cgctggcaca tgaatgactt cttccactcc 2820 ttcctgattg tgttccgcgt gctgtgtggg gagtggatag agaccatgtg ggactgtatg 2880 gaggttgctg gtcaagccat gtgccttact gtcttcatga tggtcatggt gattggaaac 2940 ctagtggtcc tgaatctctt tctggccttg cttmtgagct catttagtgc agacaacctt 3000 gcagccactg atgatgataa tgaaatgaat aatctccaaa ttgctgtgga taggatgcac 3060 aaaggagtag cttatgtgaa aagaaaaata tatgaattta ttcaacagtc cttcattagg 3120 aaacaaaaga ttttagatga aattaaacca cttgatgatc taaacaacaa gaaagacagt 3180 tgtatgtcca atcatacarc agaaattggg aaagatcttg actatcttaa agatgtaaat 3240 ggaactacaa gtggtatagg aactggcagc agtgttgaaa aatacattat tgatgaaagt 3300 gattacatgt cattcataaa caaccccagt cttactgtga ctgtaccaat tgctgtagga 3360 gaatctgact ttgaaaattt aaacacggaa gactttagta gtgaatcgga tctggaagaa 3420 agcaaagaga aactgaatga aagcagtagc tcatcagaag gtagcactgt ggacatcggc 3480 gcacctgtag aagaacagcc cgtagtggaa cctgaagaaa ctcttgaacc agaagcttgt 3540 ttcactgaag gctgtgtaca aagattcaag tgttgtcaaa tcaatgtgga agaaggcaga 3600 ggaaaacaat ggtggaacct gagaaggacg tgtttccgaa tagttgaaca taactggttt 3660 gagaccttca ttgttttcat gattctcctt agtagtggtg ctctggcatt tgaagatata 3720 tatattgatc agcgaaagac gattaagacg atgttggaat atgctgacaa ggttttcact 3780 tacattttca ttctggaaat gcttctaaaa tgggtggcat atggctatca aacatatttc 3840 accaatgcct ggtgttggct ggacttctta attgttgatg tttcattggt cagtttaaca 3900 gcaaatgcct tgggttactc agaacttgga gccatcaaat ctctcaggac actaagagct 3960 ctgagacctc taagagcctt atctcgattt gaagggatga gggtggttgt gaatgccctt 4020 ttaggagcaa ttccatccat catgaatgtg cttctggttt gtcttatatt ctggctaatt 4080 ttcagcatca tgggcgtaaa tttgtttgct ggcaaattct accactgtat taacaccaca 4140 actggtgaca ggccacattc aaaggatgga tggatataa 4179 18 1392 PRT homo sapiens VARIANT (1)...(1392) Xaa = Any Amino Acid 18 Met Glu Gln Thr Val Leu Val Pro Pro Gly Pro Asp Ser Phe Asn Phe 1 5 10 15 Phe Thr Arg Glu Ser Leu Ala Ala Ile Glu Arg Arg Ile Ala Glu Glu 20 25 30 Lys Ala Lys Asn Pro Lys Pro Asp Lys Lys Asp Asp Asp Glu Asn Gly 35 40 45 Pro Lys Pro Asn Ser Asp Leu Glu Ala Gly Lys Asn Leu Pro Phe Ile 50 55 60 Tyr Gly Asp Ile Pro Pro Glu Met Val Ser Glu Pro Leu Glu Asp Leu 65 70 75 80 Asp Pro Tyr Tyr Ile Asn Lys Lys Thr Phe Ile Val Leu Asn Lys Gly 85 90 95 Lys Ala Ile Phe Arg Phe Ser Ala Thr Ser Ala Leu Tyr Ile Leu Thr 100 105 110 Pro Phe Asn Pro Leu Arg Lys Ile Ala Ile Lys Ile Leu Val His Ser 115 120 125 Leu Phe Ser Met Leu Ile Met Cys Thr Ile Leu Thr Asn Cys Val Phe 130 135 140 Met Thr Met Ser Asn Pro Pro Asp Trp Thr Lys Asn Val Glu Tyr Thr 145 150 155 160 Phe Thr Gly Ile Tyr Thr Phe Glu Ser Leu Ile Lys Ile Ile Ala Arg 165 170 175 Gly Phe Cys Leu Glu Asp Phe Thr Phe Leu Arg Asp Pro Trp Asn Trp 180 185 190 Leu Asp Phe Thr Val Ile Thr Phe Ala Tyr Val Thr Glu Phe Val Asp 195 200 205 Leu Gly Asn Val Ser Ala Leu Arg Thr Phe Arg Val Leu Arg Ala Leu 210 215 220 Lys Thr Ile Ser Val Ile Pro Gly Leu Lys Thr Ile Val Gly Ala Leu 225 230 235 240 Ile Gln Ser Val Lys Lys Leu Ser Asp Val Met Ile Leu Thr Val Phe 245 250 255 Cys Leu Ser Val Phe Ala Leu Ile Gly Leu Gln Leu Phe Met Gly Asn 260 265 270 Leu Arg Asn Lys Cys Ile Gln Trp Pro Pro Thr Asn Ala Ser Leu Glu 275 280 285 Glu His Ser Ile Glu Lys Asn Ile Thr Val Asn Tyr Asn Gly Thr Leu 290 295 300 Ile Asn Glu Thr Val Phe Glu Phe Asp Trp Lys Ser Tyr Ile Gln Asp 305 310 315 320 Ser Arg Tyr His Tyr Phe Leu Glu Gly Phe Leu Asp Ala Leu Leu Cys 325 330 335 Gly Asn Ser Ser Asp Ala Gly Gln Cys Pro Glu Gly Tyr Met Cys Val 340 345 350 Lys Ala Gly Arg Asn Pro Asn Tyr Gly Tyr Thr Ser Phe Asp Thr Phe 355 360 365 Ser Trp Ala Phe Leu Ser Leu Phe Arg Leu Met Thr Gln Asp Phe Trp 370 375 380 Glu Asn Leu Tyr Gln Leu Thr Leu Arg Ala Ala Gly Lys Thr Tyr Met 385 390 395 400 Ile Phe Phe Val Leu Val Ile Phe Leu Gly Ser Phe Tyr Leu Ile Asn 405 410 415 Leu Ile Leu Ala Val Val Ala Met Ala Tyr Glu Glu Gln Asn Gln Ala 420 425 430 Thr Leu Glu Glu Ala Glu Gln Lys Glu Ala Glu Phe Gln Gln Met Ile 435 440 445 Glu Gln Leu Lys Lys Gln Gln Glu Ala Ala Gln Gln Ala Ala Thr Ala 450 455 460 Thr Ala Ser Glu His Ser Arg Glu Pro Ser Ala Ala Gly Arg Leu Ser 465 470 475 480 Asp Ser Ser Ser Glu Ala Ser Lys Leu Ser Ser Lys Ser Ala Lys Glu 485 490 495 Arg Arg Asn Arg Arg Lys Lys Arg Lys Gln Lys Glu Gln Ser Gly Gly 500 505 510 Glu Glu Lys Asp Glu Asp Glu Phe Gln Lys Ser Glu Ser Glu Asp Ser 515 520 525 Ile Arg Arg Lys Gly Phe Arg Phe Ser Ile Glu Gly Asn Arg Leu Thr 530 535 540 Tyr Glu Lys Arg Tyr Ser Ser Pro His Gln Ser Leu Leu Ser Ile Arg 545 550 555 560 Gly Ser Leu Phe Ser Pro Arg Arg Asn Ser Arg Thr Ser Leu Phe Ser 565 570 575 Phe Arg Gly Arg Ala Lys Asp Val Gly Ser Glu Asn Asp Phe Ala Asp 580 585 590 Asp Glu His Ser Thr Phe Glu Asp Asn Glu Ser Arg Arg Asp Ser Leu 595 600 605 Phe Val Pro Arg Arg His Gly Glu Arg Arg Asn Ser Asn Leu Ser Gln 610 615 620 Thr Ser Arg Ser Ser Arg Met Leu Ala Val Phe Pro Ala Asn Gly Lys 625 630 635 640 Met His Ser Thr Val Asp Cys Asn Gly Val Val Ser Leu Val Gly Gly 645 650 655 Pro Ser Val Pro Thr Ser Pro Val Gly Gln Leu Leu Pro Glu Val Ile 660 665 670 Ile Asp Lys Pro Ala Thr Asp Asp Asn Gly Thr Thr Thr Glu Thr Glu 675 680 685 Met Arg Lys Arg Arg Ser Ser Ser Phe His Val Ser Met Asp Phe Leu 690 695 700 Glu Asp Pro Ser Gln Arg Gln Arg Ala Met Ser Ile Ala Ser Ile Leu 705 710 715 720 Thr Asn Thr Val Glu Glu Leu Glu Glu Ser Arg Gln Lys Cys Pro Pro 725 730 735 Cys Trp Tyr Lys Phe Ser Asn Ile Phe Leu Ile Trp Asp Cys Ser Pro 740 745 750 Tyr Trp Leu Lys Val Lys His Val Val Asn Leu Val Val Met Asp Pro 755 760 765 Phe Val Asp Leu Ala Ile Thr Ile Cys Ile Val Leu Asn Thr Leu Phe 770 775 780 Met Ala Met Glu His Tyr Pro Met Thr Asp His Phe Asn Asn Val Leu 785 790 795 800 Thr Val Gly Asn Leu Val Phe Thr Gly Ile Phe Thr Ala Glu Met Phe 805 810 815 Leu Lys Ile Ile Ala Met Asp Pro Tyr Tyr Tyr Phe Gln Glu Gly Trp 820 825 830 Asn Ile Phe Asp Gly Phe Ile Val Thr Leu Ser Leu Val Glu Leu Gly 835 840 845 Leu Ala Asn Val Glu Gly Leu Ser Val Leu Arg Ser Phe Arg Leu Leu 850 855 860 Arg Val Phe Lys Leu Ala Lys Ser Trp Pro Thr Leu Asn Met Leu Ile 865 870 875 880 Lys Ile Ile Gly Asn Ser Val Gly Ala Leu Gly Asn Leu Thr Leu Val 885 890 895 Leu Ala Ile Ile Val Phe Ile Phe Ala Val Val Gly Met Gln Leu Phe 900 905 910 Gly Lys Ser Tyr Lys Asp Cys Val Cys Lys Ile Ala Ser Asp Cys Gln 915 920 925 Leu Pro Arg Trp His Met Asn Asp Phe Phe His Ser Phe Leu Ile Val 930 935 940 Phe Arg Val Leu Cys Gly Glu Trp Ile Glu Thr Met Trp Asp Cys Met 945 950 955 960 Glu Val Ala Gly Gln Ala Met Cys Leu Thr Val Phe Met Met Val Met 965 970 975 Val Ile Gly Asn Leu Val Val Leu Asn Leu Phe Leu Ala Leu Leu Xaa 980 985 990 Ser Ser Phe Ser Ala Asp Asn Leu Ala Ala Thr Asp Asp Asp Asn Glu 995 1000 1005 Met Asn Asn Leu Gln Ile Ala Val Asp Arg Met His Lys Gly Val Ala 1010 1015 1020 Tyr Val Lys Arg Lys Ile Tyr Glu Phe Ile Gln Gln Ser Phe Ile Arg 1025 1030 1035 1040 Lys Gln Lys Ile Leu Asp Glu Ile Lys Pro Leu Asp Asp Leu Asn Asn 1045 1050 1055 Lys Lys Asp Ser Cys Met Ser Asn His Thr Xaa Glu Ile Gly Lys Asp 1060 1065 1070 Leu Asp Tyr Leu Lys Asp Val Asn Gly Thr Thr Ser Gly Ile Gly Thr 1075 1080 1085 Gly Ser Ser Val Glu Lys Tyr Ile Ile Asp Glu Ser Asp Tyr Met Ser 1090 1095 1100 Phe Ile Asn Asn Pro Ser Leu Thr Val Thr Val Pro Ile Ala Val Gly 1105 1110 1115 1120 Glu Ser Asp Phe Glu Asn Leu Asn Thr Glu Asp Phe Ser Ser Glu Ser 1125 1130 1135 Asp Leu Glu Glu Ser Lys Glu Lys Leu Asn Glu Ser Ser Ser Ser Ser 1140 1145 1150 Glu Gly Ser Thr Val Asp Ile Gly Ala Pro Val Glu Glu Gln Pro Val 1155 1160 1165 Val Glu Pro Glu Glu Thr Leu Glu Pro Glu Ala Cys Phe Thr Glu Gly 1170 1175 1180 Cys Val Gln Arg Phe Lys Cys Cys Gln Ile Asn Val Glu Glu Gly Arg 1185 1190 1195 1200 Gly Lys Gln Trp Trp Asn Leu Arg Arg Thr Cys Phe Arg Ile Val Glu 1205 1210 1215 His Asn Trp Phe Glu Thr Phe Ile Val Phe Met Ile Leu Leu Ser Ser 1220 1225 1230 Gly Ala Leu Ala Phe Glu Asp Ile Tyr Ile Asp Gln Arg Lys Thr Ile 1235 1240 1245 Lys Thr Met Leu Glu Tyr Ala Asp Lys Val Phe Thr Tyr Ile Phe Ile 1250 1255 1260 Leu Glu Met Leu Leu Lys Trp Val Ala Tyr Gly Tyr Gln Thr Tyr Phe 1265 1270 1275 1280 Thr Asn Ala Trp Cys Trp Leu Asp Phe Leu Ile Val Asp Val Ser Leu 1285 1290 1295 Val Ser Leu Thr Ala Asn Ala Leu Gly Tyr Ser Glu Leu Gly Ala Ile 1300 1305 1310 Lys Ser Leu Arg Thr Leu Arg Ala Leu Arg Pro Leu Arg Ala Leu Ser 1315 1320 1325 Arg Phe Glu Gly Met Arg Val Val Val Asn Ala Leu Leu Gly Ala Ile 1330 1335 1340 Pro Ser Ile Met Asn Val Leu Leu Val Cys Leu Ile Phe Trp Leu Ile 1345 1350 1355 1360 Phe Ser Ile Met Gly Val Asn Leu Phe Ala Gly Lys Phe Tyr His Cys 1365 1370 1375 Ile Asn Thr Thr Thr Gly Asp Arg Pro His Ser Lys Asp Gly Trp Ile 1380 1385 1390 19 4197 DNA homo sapiens 19 atggagcaaa cagtgcttgt accaccagga cctgacagct tcaacttctt caccagagaa 60 tctcttgcgg ctattgaaag acgcattgca gaagaaaagg caaagaatcc caaaccagac 120 aaaaaagatg acgacgaaaa tggcccaaag ccaaatagtg acttggaagc tggaaagaac 180 cttccattta tttatggaga cattcctcca gagatggtgt cagagcccct ggaggacctg 240 gacccctact atatcaataa gaaaactttt atagtattga ataaagggaa ggccatcttc 300 cggttcagtg ccacctctgc cctgtacatt ttaactccct tcaatcctct taggaaaata 360 gctattaaga ttttggtaca ttcattattc agcatgctaa ttatgtgcac tattttgaca 420 aactgtgtgt ttatgacaat gagtaaccct cctgattgga caaagaatgt agaatacacc 480 ttcacaggaa tatatacttt tgaatcactt ataaaaatta ttgcaagggg attctgttta 540 gaagatttta ctttccttcg ggatccatgg aactggctcg atttcactgt cattacattt 600 gcgtacgtca cagagtttgt ggacctgggc aatgtctcgg cattgagaac attcagagtt 660 ctccgagcat tgaagacgat ttcagtcatt ccaggcctga aaaccattgt gggagccctg 720 atccagtctg tgaagaagct ctcagatgta atgatcctga ctgtgttctg tctgagcgta 780 tttgctctaa ttgggctgca gctgttcatg ggcaacctga ggaataaatg tatacaatgg 840 cctcccacca atgcttcctt ggaggaacat agtatagaaa agaatataac tgtgaattat 900 aatggtacac ttataaatga aactgtcttt gagtttgact ggaagtcata tattcaagat 960 tcaagatatc attatttcct ggagggtttt ttagatgcac tactatgtgg aaatagctct 1020 gatgcaggcc aatgtccaga gggatatatg tgtgtgaaag ctggtagaaa tcccaattat 1080 ggctacacaa gctttgatac cttcagttgg gcttttttgt ccttgtttcg actaatgact 1140 caggacttct gggaaaatct ttatcaactg acattacgtg ctgctgggaa aacgtacatg 1200 atattttttg tgttggtcat tttcttgggc tcattctacc taataaattt gatcctggct 1260 gtggtggcca tggcctacga ggaacagaat caggccacct tggaagaagc agaacagaaa 1320 gaggccgaat ttcagcagat gattgaacag cttaaaaagc aacaggaggc agctcagcag 1380 gcagcaacgg caactgcctc agaacattcc agagagccca gtgcagcagg caggctctca 1440 gacagctcat ctgaagcctc taagttgagt tccaagagtg ctaaggaaag aagaaatcgg 1500 aggaagaaaa gaaaacagaa agagcagtct ggtggggaag agaaagatga ggatgaattc 1560 caaaaatctg aatctgagga cagcatcagg aggaaaggtt ttcgcttctc cattgaaggg 1620 aaccgattga catatgaaaa gaggtactcc tccccacacc agtctttgtt gagcatccgt 1680 ggctccctat tttcaccaag gcgaaatagc agaacaagcc ttttcagctt tagagggcga 1740 gcaaaggatg tgggatctga gaacgacttc gcagatgatg agcacagcac ctttgaggat 1800 aacgagagcc gtagagattc cttgtttgtg ccccgacgac acggagagag acgcaacagc 1860 aacctgagtc agaccagtag gtcatcccgg atgctggcag tgtttccagc gaatgggaag 1920 atgcacagca ctgtggattg caatggtgtg gtttccttgg ttggtggacc ttcagttcct 1980 acatcgcctg ttggacagct tctgccagag gtgataatag ataagccagc tactgatgac 2040 aatggaacaa ccactgaaac tgaaatgaga aagagaaggt caagttcttt ccacgtttcc 2100 atggactttc tagaagatcc ttcccaaagg caacgagcaa tgagtatagc cagcattcta 2160 acaaatacag tagaagaact tgaagaatcc aggcagaaat gcccaccctg ttggtataaa 2220 ttttccaaca tattcttaat ctgggactgt tctccatatt ggttaaaagt gaaacatgtt 2280 gtcaacctgg tygtgatgga cccatttgtt gacctggcca tcaccatctg tattgtctta 2340 aatactcttt tcatggccat ggagcactat ccaatgacgg accatttcaa taatgtgctt 2400 acagtaggaa acttggtttt cactgggatc tttacagcag aaatgtttct gaaaattatt 2460 gccatggatc cttactatta tttccaagaa ggctggaata tctttgacgg ttttattgtg 2520 acgcttagcc tggtagaact tggactcgcc aatgtggaag gattatctgt tctccgttca 2580 tttcgattgc tgcgagtttt caagttggca aaatcttggc caacgttaaa tatgctaata 2640 aagatcatcg gcaattccgt gggggctctg ggaaatttaa ccctcgtctt ggccatcatc 2700 gtcttcattt ttgccgtggt cggcatgcag ctctttggta aaagctacaa agattgtgtc 2760 tgcaagatcg ccagtgattg tcaactccca cgctggcaca tgaatgactt cttccactcc 2820 ttcctgattg tgttccgcgt gctgtgtggg gagtggatag agaccatgtg ggactgtatg 2880 gaggttgctg gtcaagccat gtgccttact gtcttcatga tggtcatggt gattggaaac 2940 ctagtggtcc tgaatctctt tctggccttg cttmtgagct catttagtgc agacaacctt 3000 gcagccactg atgatgataa tgaaatgaat aatctccaaa ttgctgtgga taggatgcac 3060 aaaggagtag cttatgtgaa aagaaaaata tatgaattta ttcaacagtc cttcattagg 3120 aaacaaaaga ttttagatga aattaaacca cttgatgatc taaacaacaa gaaagacagt 3180 tgtatgtcca atcatacarc agaaattggg aaagatcttg actatcttaa agatgtaaat 3240 ggaactacaa gtggtatagg aactggcagc agtgttgaaa aatacattat tgatgaaagt 3300 gattacatgt cattcataaa caaccccagt cttactgtga ctgtaccaat tgctgtagga 3360 gaatctgact ttgaaaattt aaacacggaa gactttagta gtgaatcgga tctggaagaa 3420 agcaaagaga aactgaatga aagcagtagc tcatcagaag gtagcactgt ggacatcggc 3480 gcacctgtag aagaacagcc cgtagtggaa cctgaagaaa ctcttgaacc agaagcttgt 3540 ttcactgaag gctgtgtaca aagattcaag tgttgtcaaa tcaatgtgga agaaggcaga 3600 ggaaaacaat ggtggaacct gagaaggacg tgtttccgaa tagttgaaca taactggttt 3660 gagaccttca ttgttttcat gattctcctt agtagtggtg ctctggcatt tgaagatata 3720 tatattgatc agcgaaagac gattaagacg atgttggaat atgctgacaa ggttttcact 3780 tacattttca ttctggaaat gcttctaaaa tgggtggcat atggctatca aacatatttc 3840 accaatgcct ggtgttggct ggacttctta attgttgatg tttcattggt cagtttaaca 3900 gcaaatgcct tgggttactc agaacttgga gccatcaaat ctctcaggac actaagagct 3960 ctgagacctc taagagcctt atctcgattt gaagggatga gggataatct tgctccaact 4020 tggatggggt ggagcgctgg ttcctcccct gagcccttta ttatgggtgg ttgtgaatgc 4080 ccttttagga gcaattccat ccatcatgaa tgtgcttctg gtttgtctta tattctggct 4140 aattttcagc atcatgggcg taaatttgtt tgctggcaaa ttctaccact gtattaa 4197 20 1398 PRT homo sapiens VARIANT (1)...(1398) Xaa = Any Amino Acid 20 Met Glu Gln Thr Val Leu Val Pro Pro Gly Pro Asp Ser Phe Asn Phe 1 5 10 15 Phe Thr Arg Glu Ser Leu Ala Ala Ile Glu Arg Arg Ile Ala Glu Glu 20 25 30 Lys Ala Lys Asn Pro Lys Pro Asp Lys Lys Asp Asp Asp Glu Asn Gly 35 40 45 Pro Lys Pro Asn Ser Asp Leu Glu Ala Gly Lys Asn Leu Pro Phe Ile 50 55 60 Tyr Gly Asp Ile Pro Pro Glu Met Val Ser Glu Pro Leu Glu Asp Leu 65 70 75 80 Asp Pro Tyr Tyr Ile Asn Lys Lys Thr Phe Ile Val Leu Asn Lys Gly 85 90 95 Lys Ala Ile Phe Arg Phe Ser Ala Thr Ser Ala Leu Tyr Ile Leu Thr 100 105 110 Pro Phe Asn Pro Leu Arg Lys Ile Ala Ile Lys Ile Leu Val His Ser 115 120 125 Leu Phe Ser Met Leu Ile Met Cys Thr Ile Leu Thr Asn Cys Val Phe 130 135 140 Met Thr Met Ser Asn Pro Pro Asp Trp Thr Lys Asn Val Glu Tyr Thr 145 150 155 160 Phe Thr Gly Ile Tyr Thr Phe Glu Ser Leu Ile Lys Ile Ile Ala Arg 165 170 175 Gly Phe Cys Leu Glu Asp Phe Thr Phe Leu Arg Asp Pro Trp Asn Trp 180 185 190 Leu Asp Phe Thr Val Ile Thr Phe Ala Tyr Val Thr Glu Phe Val Asp 195 200 205 Leu Gly Asn Val Ser Ala Leu Arg Thr Phe Arg Val Leu Arg Ala Leu 210 215 220 Lys Thr Ile Ser Val Ile Pro Gly Leu Lys Thr Ile Val Gly Ala Leu 225 230 235 240 Ile Gln Ser Val Lys Lys Leu Ser Asp Val Met Ile Leu Thr Val Phe 245 250 255 Cys Leu Ser Val Phe Ala Leu Ile Gly Leu Gln Leu Phe Met Gly Asn 260 265 270 Leu Arg Asn Lys Cys Ile Gln Trp Pro Pro Thr Asn Ala Ser Leu Glu 275 280 285 Glu His Ser Ile Glu Lys Asn Ile Thr Val Asn Tyr Asn Gly Thr Leu 290 295 300 Ile Asn Glu Thr Val Phe Glu Phe Asp Trp Lys Ser Tyr Ile Gln Asp 305 310 315 320 Ser Arg Tyr His Tyr Phe Leu Glu Gly Phe Leu Asp Ala Leu Leu Cys 325 330 335 Gly Asn Ser Ser Asp Ala Gly Gln Cys Pro Glu Gly Tyr Met Cys Val 340 345 350 Lys Ala Gly Arg Asn Pro Asn Tyr Gly Tyr Thr Ser Phe Asp Thr Phe 355 360 365 Ser Trp Ala Phe Leu Ser Leu Phe Arg Leu Met Thr Gln Asp Phe Trp 370 375 380 Glu Asn Leu Tyr Gln Leu Thr Leu Arg Ala Ala Gly Lys Thr Tyr Met 385 390 395 400 Ile Phe Phe Val Leu Val Ile Phe Leu Gly Ser Phe Tyr Leu Ile Asn 405 410 415 Leu Ile Leu Ala Val Val Ala Met Ala Tyr Glu Glu Gln Asn Gln Ala 420 425 430 Thr Leu Glu Glu Ala Glu Gln Lys Glu Ala Glu Phe Gln Gln Met Ile 435 440 445 Glu Gln Leu Lys Lys Gln Gln Glu Ala Ala Gln Gln Ala Ala Thr Ala 450 455 460 Thr Ala Ser Glu His Ser Arg Glu Pro Ser Ala Ala Gly Arg Leu Ser 465 470 475 480 Asp Ser Ser Ser Glu Ala Ser Lys Leu Ser Ser Lys Ser Ala Lys Glu 485 490 495 Arg Arg Asn Arg Arg Lys Lys Arg Lys Gln Lys Glu Gln Ser Gly Gly 500 505 510 Glu Glu Lys Asp Glu Asp Glu Phe Gln Lys Ser Glu Ser Glu Asp Ser 515 520 525 Ile Arg Arg Lys Gly Phe Arg Phe Ser Ile Glu Gly Asn Arg Leu Thr 530 535 540 Tyr Glu Lys Arg Tyr Ser Ser Pro His Gln Ser Leu Leu Ser Ile Arg 545 550 555 560 Gly Ser Leu Phe Ser Pro Arg Arg Asn Ser Arg Thr Ser Leu Phe Ser 565 570 575 Phe Arg Gly Arg Ala Lys Asp Val Gly Ser Glu Asn Asp Phe Ala Asp 580 585 590 Asp Glu His Ser Thr Phe Glu Asp Asn Glu Ser Arg Arg Asp Ser Leu 595 600 605 Phe Val Pro Arg Arg His Gly Glu Arg Arg Asn Ser Asn Leu Ser Gln 610 615 620 Thr Ser Arg Ser Ser Arg Met Leu Ala Val Phe Pro Ala Asn Gly Lys 625 630 635 640 Met His Ser Thr Val Asp Cys Asn Gly Val Val Ser Leu Val Gly Gly 645 650 655 Pro Ser Val Pro Thr Ser Pro Val Gly Gln Leu Leu Pro Glu Val Ile 660 665 670 Ile Asp Lys Pro Ala Thr Asp Asp Asn Gly Thr Thr Thr Glu Thr Glu 675 680 685 Met Arg Lys Arg Arg Ser Ser Ser Phe His Val Ser Met Asp Phe Leu 690 695 700 Glu Asp Pro Ser Gln Arg Gln Arg Ala Met Ser Ile Ala Ser Ile Leu 705 710 715 720 Thr Asn Thr Val Glu Glu Leu Glu Glu Ser Arg Gln Lys Cys Pro Pro 725 730 735 Cys Trp Tyr Lys Phe Ser Asn Ile Phe Leu Ile Trp Asp Cys Ser Pro 740 745 750 Tyr Trp Leu Lys Val Lys His Val Val Asn Leu Val Val Met Asp Pro 755 760 765 Phe Val Asp Leu Ala Ile Thr Ile Cys Ile Val Leu Asn Thr Leu Phe 770 775 780 Met Ala Met Glu His Tyr Pro Met Thr Asp His Phe Asn Asn Val Leu 785 790 795 800 Thr Val Gly Asn Leu Val Phe Thr Gly Ile Phe Thr Ala Glu Met Phe 805 810 815 Leu Lys Ile Ile Ala Met Asp Pro Tyr Tyr Tyr Phe Gln Glu Gly Trp 820 825 830 Asn Ile Phe Asp Gly Phe Ile Val Thr Leu Ser Leu Val Glu Leu Gly 835 840 845 Leu Ala Asn Val Glu Gly Leu Ser Val Leu Arg Ser Phe Arg Leu Leu 850 855 860 Arg Val Phe Lys Leu Ala Lys Ser Trp Pro Thr Leu Asn Met Leu Ile 865 870 875 880 Lys Ile Ile Gly Asn Ser Val Gly Ala Leu Gly Asn Leu Thr Leu Val 885 890 895 Leu Ala Ile Ile Val Phe Ile Phe Ala Val Val Gly Met Gln Leu Phe 900 905 910 Gly Lys Ser Tyr Lys Asp Cys Val Cys Lys Ile Ala Ser Asp Cys Gln 915 920 925 Leu Pro Arg Trp His Met Asn Asp Phe Phe His Ser Phe Leu Ile Val 930 935 940 Phe Arg Val Leu Cys Gly Glu Trp Ile Glu Thr Met Trp Asp Cys Met 945 950 955 960 Glu Val Ala Gly Gln Ala Met Cys Leu Thr Val Phe Met Met Val Met 965 970 975 Val Ile Gly Asn Leu Val Val Leu Asn Leu Phe Leu Ala Leu Leu Xaa 980 985 990 Ser Ser Phe Ser Ala Asp Asn Leu Ala Ala Thr Asp Asp Asp Asn Glu 995 1000 1005 Met Asn Asn Leu Gln Ile Ala Val Asp Arg Met His Lys Gly Val Ala 1010 1015 1020 Tyr Val Lys Arg Lys Ile Tyr Glu Phe Ile Gln Gln Ser Phe Ile Arg 1025 1030 1035 1040 Lys Gln Lys Ile Leu Asp Glu Ile Lys Pro Leu Asp Asp Leu Asn Asn 1045 1050 1055 Lys Lys Asp Ser Cys Met Ser Asn His Thr Xaa Glu Ile Gly Lys Asp 1060 1065 1070 Leu Asp Tyr Leu Lys Asp Val Asn Gly Thr Thr Ser Gly Ile Gly Thr 1075 1080 1085 Gly Ser Ser Val Glu Lys Tyr Ile Ile Asp Glu Ser Asp Tyr Met Ser 1090 1095 1100 Phe Ile Asn Asn Pro Ser Leu Thr Val Thr Val Pro Ile Ala Val Gly 1105 1110 1115 1120 Glu Ser Asp Phe Glu Asn Leu Asn Thr Glu Asp Phe Ser Ser Glu Ser 1125 1130 1135 Asp Leu Glu Glu Ser Lys Glu Lys Leu Asn Glu Ser Ser Ser Ser Ser 1140 1145 1150 Glu Gly Ser Thr Val Asp Ile Gly Ala Pro Val Glu Glu Gln Pro Val 1155 1160 1165 Val Glu Pro Glu Glu Thr Leu Glu Pro Glu Ala Cys Phe Thr Glu Gly 1170 1175 1180 Cys Val Gln Arg Phe Lys Cys Cys Gln Ile Asn Val Glu Glu Gly Arg 1185 1190 1195 1200 Gly Lys Gln Trp Trp Asn Leu Arg Arg Thr Cys Phe Arg Ile Val Glu 1205 1210 1215 His Asn Trp Phe Glu Thr Phe Ile Val Phe Met Ile Leu Leu Ser Ser 1220 1225 1230 Gly Ala Leu Ala Phe Glu Asp Ile Tyr Ile Asp Gln Arg Lys Thr Ile 1235 1240 1245 Lys Thr Met Leu Glu Tyr Ala Asp Lys Val Phe Thr Tyr Ile Phe Ile 1250 1255 1260 Leu Glu Met Leu Leu Lys Trp Val Ala Tyr Gly Tyr Gln Thr Tyr Phe 1265 1270 1275 1280 Thr Asn Ala Trp Cys Trp Leu Asp Phe Leu Ile Val Asp Val Ser Leu 1285 1290 1295 Val Ser Leu Thr Ala Asn Ala Leu Gly Tyr Ser Glu Leu Gly Ala Ile 1300 1305 1310 Lys Ser Leu Arg Thr Leu Arg Ala Leu Arg Pro Leu Arg Ala Leu Ser 1315 1320 1325 Arg Phe Glu Gly Met Arg Asp Asn Leu Ala Pro Thr Trp Met Gly Trp 1330 1335 1340 Ser Ala Gly Ser Ser Pro Glu Pro Phe Ile Met Gly Gly Cys Glu Cys 1345 1350 1355 1360 Pro Phe Arg Ser Asn Ser Ile His His Glu Cys Ala Ser Gly Leu Ser 1365 1370 1375 Tyr Ile Leu Ala Asn Phe Gln His His Gly Arg Lys Phe Val Cys Trp 1380 1385 1390 Gln Ile Leu Pro Leu Tyr 1395

Claims

What is claimed is:

1. An isolated nucleic acid molecule comprising a nucleotide sequence encoding an amino acid sequence drawn from the group consisting of SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20.

2. An isolated nucleic acid molecule comprising a nucleotide sequence that:

(a) encodes the amino acid sequence shown in SEQ ID NO: 12; and

(b) hybridizes under stringent conditions to the nucleotide sequence of SEQ ID NO: 11 or the complement thereof.

3. An isolated nucleic acid molecule comprising a nucleotide sequence encoding the amino acid sequence shown in SEQ ID NO: 12.

4. The isolated nucleic acid of claim 3 wherein said nucleic acid is a cDNA or PCR product.

5. An isolated oligopeptide having a sequence of at least about 12 contiguous amino acids first disclosed in SEQ ID NO:12.